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Science 314 (5800): 825-828

Copyright © 2006 by the American Association for the Advancement of Science

Transgenic Mice with a Reduced Core Body Temperature Have an Increased Life Span

Bruno Conti,1,2* Manuel Sanchez-Alavez,1,2 Raphaelle Winsky-Sommerer,3{dagger} Maria Concetta Morale,1{ddagger} Jacinta Lucero,1,2 Sara Brownell,1,2§ Veronique Fabre,3|| Salvador Huitron-Resendiz,2 Steven Henriksen,2 Eric P. Zorrilla,1,2 Luis de Lecea,3# Tamas Bartfai1,2

Abstract: Reduction of core body temperature has been proposed to contribute to the increased life span and the antiaging effects conferred by calorie restriction (CR). Validation of this hypothesis has been difficult in homeotherms, primarily due to a lack of experimental models. We report that transgenic mice engineered to overexpress the uncoupling protein 2 in hypocretin neurons (Hcrt-UCP2) have elevated hypothalamic temperature. The effects of local temperature elevation on the central thermostat resulted in a 0.3° to 0.5°C reduction of the core body temperature. Fed ad libitum, Hcrt-UCP2 transgenic mice had the same caloric intake as their wild-type littermates but had increased energy efficiency and a greater median life span (12% increase in males; 20% increase in females). Thus, modest, sustained reduction of core body temperature prolonged life span independent of altered diet or CR.

1 Harold L. Dorris Neurological Research Center, Scripps Research Institute, La Jolla, CA 92037, USA.
2 Molecular and Integrative Neurosciences Department, Scripps Research Institute, La Jolla, CA 92037, USA.
3 Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.

{dagger} Present address: Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.

{ddagger} Present address: Dipartimento di Neurofarmacologia, OASI (IRCCS), Troina, Italy.

§ Division of Geriatric Medicine, Department of Medicine, UCSD, La Jolla, CA 92037, USA.

|| Present address: Unité Mixte de Recherche 677, Institut National de la Santé et de la Recherche Médicale/Universite Pierre et Marie Curie, Paris, France.

Present address: Western University of Health Sciences, Pomona, CA 91766, USA.

# Present address: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94305, USA.

* To whom correspondence should be addressed. E mail: bconti{at}scripps.edu

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