title: Uncoupling protein 2 protects mice from aging.
abstract: Uncoupling protein (UCP) 2 is a mitochondrial transporter protein that plays various roles in cellular metabolism, including the glucose and lipid metabolism. Polymorphisms in UCP2 are associated with longevity in humans. In line with this, mice carrying the UCP2 transgene under the control of hypocretin promoter were reported to have an extended lifespan, while, conversely, mice deficient in Ucp2 demonstrated a significantly shorter lifespan. In this study, we examined the phenotype of aging in a large colony of Ucp2-deficient (Ucp2(-/-)) mice on the molecular level. We have found that the significantly shorter lives of Ucp2(-/-) mice is the result of an accelerated aging process throughout their entire lifespan. Thus, Ucp2(-/-) mice not only earlier gained sexual maturity, but also earlier progressed into an aging phenotype, reflected by a decrease in body weight, increased neutrophil numbers, and earlier emergence of spontaneous ulcerative dermatitis. Intriguingly, on the molecular level this acceleration in aging predominantly driven by increased levels of circulating IGF-1 in Ucp2(-/-) mice, hinting at a crosstalk between UCP2 and the classical Insulin/IGF-1 signaling aging pathway.
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany. Electronic address: Misa.Hirose@uksh.de.
authors.forename: Misa
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Schilf
authors.affiliation: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Lange
authors.affiliation: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Mayer
authors.affiliation: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Reichart
authors.affiliation: Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
authors.forename: Pallab
authors.initials: P
authors.lastname: Maity
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Jöhren
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaninger
authors.affiliation: Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
authors.affiliation: Molecular Gastroenterology, University Clinic Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sina
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Sadik
authors.affiliation: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
authors.affiliation: Institute of Physical and Chemical Biology, UMR 7099, CNRS, University Paris-Diderot, Sorbonne Paris Cités, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Miroux
authors.affiliation: Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany. Electronic address: Saleh.Ibrahim@uksh.de.
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ibrahim
mesh_terms: D000375:Aging; D000818:Animals; D003430:Cross-Sectional Studies; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D044967:Serum / Q000737:chemistry; D000071246:Uncoupling Protein 2 / Q000172:deficiency / Q000378:metabolism*
chemical_list: C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I
keywords: Insulin/IGF-1 pathway; Lifespan; Metabolism; Premature aging; UCP2