Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease.
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.
Gates
Allison C
AC
Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Bernal-Mizrachi
Carlos
C
Chinault
Sharon L
SL
Feng
Chu
C
Schneider
Jochen G
JG
Coleman
Trey
T
Malone
James P
JP
Townsend
R Reid
RR
Chakravarthy
Manu V
MV
Semenkovich
Clay F
CF
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D004036:Diet, Atherogenic; D004579:Electron Transport / Q000502:physiology*; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D014475:Uncoupling Agents / Q000378:metabolism; D000071256:Uncoupling Protein 1
D001057:Apolipoproteins E; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1