TY - JOUR
T1 - Uncoupling protein 2 protects mice from aging
AU - Hirose, Misa
AU - Schilf, Paul
AU - Lange, Falko
AU - Mayer, Johannes
AU - Reichart, Gesine
AU - Maity, Pallab
AU - Jöhren, Olaf
AU - Schwaninger, Markus
AU - Scharffetter-Kochanek, Karin
AU - Sina, Christian
AU - Sadik, Christian D.
AU - Köhling, Rüdiger
AU - Miroux, Bruno
AU - Ibrahim, Saleh M.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.mito.2016.06.004
DO - 10.1016/j.mito.2016.06.004
M3 - Journal articles
C2 - 27364833
SN - 1872-8278
VL - 30
SP - 42
EP - 50
JO - Mitochondrion
JF - Mitochondrion
ER -
