TY - JOUR
T1 - Transgenic mice with a reduced core body temperature have an increased life span
AU - Conti, Bruno
AU - Sanchez-Alavez, Manuel
AU - Winsky-Sommerer, Raphaelle
AU - Morale, Maria Concetta
AU - Lucero, Jacinta
AU - Brownell, Sara
AU - Fabre, Veronique
AU - Huitron-Resendiz, Salvador
AU - Henriksen, Steven
AU - Zorrilla, Eric P.
AU - De Lecea, Luis
AU - Bartfai, Tamas
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/11/3
Y1 - 2006/11/3
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1132191
DO - 10.1126/science.1132191
M3 - Article
C2 - 17082459
AN - SCOPUS:33750681712
SN - 0036-8075
VL - 314
SP - 825
EP - 828
JO - Science
JF - Science
IS - 5800
ER -