title: Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1α.
abstract: Aged skeletal muscle demonstrates declines in muscle mass and deterioration of mitochondrial content and function. Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) plays an important role in promoting muscle mitochondrial biogenesis in response to exercise training, but its role in senescent muscle is not clear. In the present study we hypothesize that a downregulation of the PGC-1α signaling pathway contributes to mitochondrial deterioration in aged muscle whereas endurance training ameliorates the deficits. Three groups of Fischer 344/BNF1 rats were used: young, sedentary (Y, 4 months); old, sedentary (O, 22 months); and old trained (OT, 22 months), subjected to treadmill running at 17.5 m/min, 10% grade for 45 min/day, 5 days/week for 12-weeks. PGC-1α mRNA and nuclear PGC-1α protein content in the soleus muscle were both decreased in O vs. Y rats, whereas OT rats showed a 2.3 and 1.8-fold higher PGC-1α content than O and Y rats, respectively (P<0.01). Mitochondrial transcription factor A (Tfam), cytochrome c (Cyt c) and mitochondrial (mt) DNA contents were significantly decreased in O vs. Y rats, but elevated by 2.2 (P<0.01), 1.4 (P<0.05) and 2.4-fold (P<0.01), respectively, in OT vs. O rats. In addition, Tfam and mtDNA showed 1.6 and 1.8-fold (P<0.01) higher levels, respectively, in OT vs. Y rats. These adaptations were accompanied by significant increases in the expression of the phosphorylated form of AMP-activated kinase (AMPK) (P<0.01), p38 mitogen-activated kinase (MAPK) (P<0.05) and silent mating type information regulator 2 homolog 1 (SIRT1) (P<0.01) in OT rats. Furthermore, OT rats showed great levels of phosphorylation in cAMP responsive element binding protein (p-CREB) and DNA binding compared to O and Y rats. These data indicate that endurance training can attenuate aging-associated decline in mitochondrial protein synthesis in skeletal muscle partly due to upregulation of PGC-1α signaling.
authors.affiliation: The Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota at Twin Cities, Minneapolis, MN 55455, USA; The Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Chounghun
authors.initials: C
authors.lastname: Kang
authors.forename: Eunhee
authors.initials: E
authors.lastname: Chung
authors.forename: Gary
authors.initials: G
authors.lastname: Diffee
authors.forename: Li Li
authors.initials: LL
authors.lastname: Ji
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; C489030:Tfam protein, rat; D014157:Transcription Factors; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: Aging; Exercise; Mitochondria; PGC-1α; Skeletal muscle