title: Transgenic mice with a reduced core body temperature have an increased life span.
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 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.
authors.affiliation: Harold L. Dorris Neurological Research Center, Scripps Research Institute, La Jolla, CA 92037, USA. bconti@scripps.edu
authors.forename: Bruno
authors.initials: B
authors.lastname: Conti
authors.forename: Manuel
authors.initials: M
authors.lastname: Sanchez-Alavez
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Winsky-Sommerer
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Morale
authors.forename: Jacinta
authors.initials: J
authors.lastname: Lucero
authors.forename: Sara
authors.initials: S
authors.lastname: Brownell
authors.forename: Veronique
authors.initials: V
authors.lastname: Fabre
authors.forename: Salvador
authors.initials: S
authors.lastname: Huitron-Resendiz
authors.forename: Steven
authors.initials: S
authors.lastname: Henriksen
authors.forename: Eric P
authors.initials: EP
authors.lastname: Zorrilla
authors.forename: Luis
authors.initials: L
authors.lastname: de Lecea
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
mesh_terms: 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
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009479:Neuropeptides; D000068797:Orexins; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2