Transgenic mice with a reduced core body temperature have an increased life span.
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 degrees to 0.5 degrees 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.
Conti
Bruno
B
Harold L. Dorris Neurological Research Center, Scripps Research Institute, La Jolla, CA 92037, USA. bconti@scripps.edu
Sanchez-Alavez
Manuel
M
Winsky-Sommerer
Raphaelle
R
Morale
Maria Concetta
MC
Lucero
Jacinta
J
Brownell
Sara
S
Fabre
Veronique
V
Huitron-Resendiz
Salvador
S
Henriksen
Steven
S
Zorrilla
Eric P
EP
de Lecea
Luis
L
Bartfai
Tamas
T
D000375:Aging; D000818:Animals; D001831:Body Temperature; D001833:Body Temperature Regulation; D001835:Body Weight; D002940:Circadian Rhythm; D004326:Drinking; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000502:physiology; D008136:Longevity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins; D011301:Preoptic Area / Q000166:cytology / Q000502:physiology*; D022722:Thermogenesis; D000071246:Uncoupling Protein 2
D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009479:Neuropeptides; D000068797:Orexins; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2