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Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1α.
Exp Gerontol. 2013 Nov; 48(11):1343-50.EG

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+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23994518

Citation

Kang, Chounghun, et al. "Exercise Training Attenuates Aging-associated Mitochondrial Dysfunction in Rat Skeletal Muscle: Role of PGC-1α." Experimental Gerontology, vol. 48, no. 11, 2013, pp. 1343-50.
Kang C, Chung E, Diffee G, et al. Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1α. Exp Gerontol. 2013;48(11):1343-50.
Kang, C., Chung, E., Diffee, G., & Ji, L. L. (2013). Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1α. Experimental Gerontology, 48(11), 1343-50. https://doi.org/10.1016/j.exger.2013.08.004
Kang C, et al. Exercise Training Attenuates Aging-associated Mitochondrial Dysfunction in Rat Skeletal Muscle: Role of PGC-1α. Exp Gerontol. 2013;48(11):1343-50. PubMed PMID: 23994518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1α. AU - Kang,Chounghun, AU - Chung,Eunhee, AU - Diffee,Gary, AU - Ji,Li Li, Y1 - 2013/08/30/ PY - 2013/05/22/received PY - 2013/07/17/revised PY - 2013/08/13/accepted PY - 2013/9/3/entrez PY - 2013/9/3/pubmed PY - 2014/6/3/medline KW - Aging KW - Exercise KW - Mitochondria KW - PGC-1α KW - Skeletal muscle SP - 1343 EP - 50 JF - Experimental gerontology JO - Exp. Gerontol. VL - 48 IS - 11 N2 - 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. SN - 1873-6815 UR - https://www.unboundmedicine.com/medline/citation/23994518/Exercise_training_attenuates_aging_associated_mitochondrial_dysfunction_in_rat_skeletal_muscle:_role_of_PGC_1α_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0531-5565(13)00267-2 DB - PRIME DP - Unbound Medicine ER -