PGC-1alpha is required for training-induced prevention of age-associated decline in mitochondrial enzymes in mouse skeletal muscle.
The aim of the present study was to test the hypothesis that exercise training prevents an age-associated decline in skeletal muscle mitochondrial enzymes through a PGC-1alpha dependent mechanism. Whole body PGC-1alpha knock-out (KO) and littermate wildtype (WT) mice were submitted to long term running wheel exercise training or a sedentary lifestyle from 2 to 13 month of age. Furthermore, a group of approximately 4-month-old mice was used as young untrained controls. There was in both genotypes an age-associated approximately 30% decrease in citrate synthase (CS) activity and superoxide dismutase (SOD)2 protein content in 13-month-old untrained mice compared with young untrained mice. However, training prevented the age-associated decrease in CS activity and SOD2 protein content only in WT mice, but long term exercise training did increase HKII protein content in both genotypes. In addition, while CS activity and protein expression of cytc and SOD2 were 50-150% lower in skeletal muscle of PGC-1alpha mice than WT mice, the expression of the pro-apoptotic protein Bax and the anti-apoptotic Bcl2 was approximately 30% elevated in PGC-1alpha KO mice. In conclusion, the present findings indicate that PGC-1alpha is required for training-induced prevention of an age-associated decline in CS activity and SOD2 protein expression in skeletal muscle.
Leick
Lotte
L
Centre of Inflammation and Metabolism & Copenhagen Muscle Research Centre, Department of Biology, Section of Molecular, Integrative Physiology, University of Copenhagen, Copenhagen, Denmark.
Lyngby
Stine Secher
SS
Wojtaszewski
Jørgen F P
JF
Wojtasewski
Jørgen F P
JF
Pilegaard
Henriette
H
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D051275:Glucose Transporter Type 4 / Q000032:analysis; D006593:Hexokinase / Q000378:metabolism; D051379:Mice; D008931:Mitochondria, Muscle / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000201:enzymology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D013482:Superoxide Dismutase / Q000032:analysis; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein / Q000032:analysis; D000099156:Superoxide Dismutase 2
D015094:3-Hydroxyacyl CoA Dehydrogenases; D002950:Citrate (si)-Synthase; D045304:Cytochromes c; D051275:Glucose Transporter Type 4; D006593:Hexokinase; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D013482:Superoxide Dismutase; D015534:Trans-Activators; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D000099156:Superoxide Dismutase 2; C494827:Bax protein, mouse; C485290:Ppargc1a protein, mouse; C495693:Slc2a4 protein, mouse