TY - JOUR
T1 - Respiratory Uncoupling in Skeletal Muscle Delays Death and Diminishes Age-Related Disease
AU - Gates, Allison C.
AU - Bernal-Mizrachi, Carlos
AU - Chinault, Sharon L.
AU - Feng, Chu
AU - Schneider, Jochen G.
AU - Coleman, Trey
AU - Malone, James P.
AU - Townsend, R. Reid
AU - Chakravarthy, Manu V.
AU - Semenkovich, Clay F.
N1 - Funding Information:
This work was supported by grants from the NIH (AG20091, P50 HL083762, and DK076729) and the Clinical Nutrition Research Unit (DK56341), Diabetes Research and Training Center (DK20579), and Digestive Diseases Research Core Center (DK52574) at Washington University. C.B-M. and M.V.C. were supported by a mentor-based postdoctoral fellowship from the American Diabetes Association. We thank J. Gordon and P. Turnbaugh for help with bomb calorimetry and P. Antin for the 1256[3Emut]MCK mice.
PY - 2007/12/5
Y1 - 2007/12/5
N2 - Age-related disease, not aging per se, causes most morbidity in older humans. Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression diminishes age-related disease in three mouse models. In a longevity study, median survival was increased in UCP mice (animals with skeletal muscle-specific UCP1 expression), and lymphoma was detected less frequently in UCP female mice. In apoE null mice, a vascular disease model, diet-induced atherosclerosis was decreased in UCP animals. In agouti yellow mice, a genetic obesity model, diabetes and hypertension were reversed by induction of UCP1 in skeletal muscle. Uncoupled mice had decreased adiposity, increased temperature and metabolic rate, elevated muscle SIRT and AMP kinase, and serum characterized by increased adiponectin and decreased IGF-1 and fibrinogen. Accelerating metabolism in skeletal muscle does not appear to impact aging but may delay age-related disease.
AB - Age-related disease, not aging per se, causes most morbidity in older humans. Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression diminishes age-related disease in three mouse models. In a longevity study, median survival was increased in UCP mice (animals with skeletal muscle-specific UCP1 expression), and lymphoma was detected less frequently in UCP female mice. In apoE null mice, a vascular disease model, diet-induced atherosclerosis was decreased in UCP animals. In agouti yellow mice, a genetic obesity model, diabetes and hypertension were reversed by induction of UCP1 in skeletal muscle. Uncoupled mice had decreased adiposity, increased temperature and metabolic rate, elevated muscle SIRT and AMP kinase, and serum characterized by increased adiponectin and decreased IGF-1 and fibrinogen. Accelerating metabolism in skeletal muscle does not appear to impact aging but may delay age-related disease.
KW - HUMDISEASE
UR - http://www.scopus.com/inward/record.url?scp=36448950118&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2007.10.010
DO - 10.1016/j.cmet.2007.10.010
M3 - Article
C2 - 18054318
AN - SCOPUS:36448950118
SN - 1550-4131
VL - 6
SP - 497
EP - 505
JO - Cell Metabolism
JF - Cell Metabolism
IS - 6
ER -