Uncoupling protein-2 regulates lifespan in mice.
The long-term effects of uncoupled mitochondrial respiration by uncoupling protein-2 (UCP2) in mammalian physiology remain controversial. Here we show that increased mitochondrial uncoupling activity of different tissues predicts longer lifespan of rats compared with mice. UCP2 reduces reactive oxygen species (ROS) production and oxidative stress throughout the aging process in different tissues in mice. The absence of UCP2 shortens lifespan in wild-type mice, and the level of UCP2 positively correlates with the postnatal survival of superoxide dismutase-2 mutant animals. Thus UCP2 has a beneficial influence on cell and tissue function leading to increased lifespan.
Andrews
Zane B
ZB
Section of Comparative Medicine, Department of Obstretics, Yale University School of Medicine, 375 Congress Ave., LSOG 117, New Haven, CT 06519, USA. zane.andrews@med.monash.edu.au
Horvath
Tamas L
TL
D000818:Animals; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008136:Longevity / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress / Q000235:genetics; D010101:Oxygen Consumption / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D012119:Respiration / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology; D016019:Survival Analysis; D000071246:Uncoupling Protein 2; D000099156:Superoxide Dismutase 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000071246:Uncoupling Protein 2; D000099156:Superoxide Dismutase 2; C000604390:Ucp2 protein, mouse; C000604391:Ucp2 protein, rat