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Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice; impact of PGC-1α.
Exp Gerontol 2013; 48(11):1311-8EG

Abstract

BACKGROUND

The present study tested the hypothesis that lifelong resveratrol (RSV) supplementation counteracts an age-associated decrease in skeletal muscle oxidative capacity through peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and that RSV combined with lifelong exercise training (EX) exerts additive effects through PGC-1α in mice.

METHODS

3 month old PGC-1α whole body knockout (KO) and wild type (WT) littermate mice were placed in cages with or without running wheel and fed either standard chow or standard chow with RSV supplementation (4 g/kg food) for 12 months. Young (3 months of age), sedentary mice on standard chow served as young controls. A graded running performance test and a glucose tolerance test were performed 2 and 1 week, respectively, before euthanization where quadriceps and extensor digitorum longus (EDL) muscles were removed.

RESULTS

In PGC-1α KO mice, quadriceps citrate synthase (CS) activity, mitochondrial (mt)DNA content as well as pyruvate dehydrogenase (PDH)-E1α, cytochrome (Cyt) c and vascular endothelial growth factor (VEGF) protein content were 20-75% lower and, EDL capillary-to-fiber (C:F) ratio was 15-30% lower than in WT mice. RSV and/or EX had no effect on the C:F ratio in EDL. CS activity (P=0.063) and mtDNA content (P=0.013) decreased with age in WT mice, and CS activity, mtDNA content, PDH-E1α protein and VEGF protein increased ~1.5-1.8-fold with lifelong EX in WT, but not in PGC-1α KO mice, while RSV alone had no significant effect on these proteins.

CONCLUSION

Lifelong EX increased activity/content of oxidative proteins, mtDNA and angiogenic proteins in skeletal muscle through PGC-1α, while RSV supplementation alone had no effect. Combining lifelong EX and RSV supplementation had no additional effect on skeletal muscle oxidative and angiogenic proteins.

Authors+Show Affiliations

Centre of Inflammation and Metabolism, August Krogh Centre, Department of Biology, August Krogh Building, University of Copenhagen, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23994519

Citation

Ringholm, Stine, et al. "Effect of Lifelong Resveratrol Supplementation and Exercise Training On Skeletal Muscle Oxidative Capacity in Aging Mice; Impact of PGC-1α." Experimental Gerontology, vol. 48, no. 11, 2013, pp. 1311-8.
Ringholm S, Olesen J, Pedersen JT, et al. Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice; impact of PGC-1α. Exp Gerontol. 2013;48(11):1311-8.
Ringholm, S., Olesen, J., Pedersen, J. T., Brandt, C. T., Halling, J. F., Hellsten, Y., ... Pilegaard, H. (2013). Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice; impact of PGC-1α. Experimental Gerontology, 48(11), pp. 1311-8. doi:10.1016/j.exger.2013.08.012.
Ringholm S, et al. Effect of Lifelong Resveratrol Supplementation and Exercise Training On Skeletal Muscle Oxidative Capacity in Aging Mice; Impact of PGC-1α. Exp Gerontol. 2013;48(11):1311-8. PubMed PMID: 23994519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice; impact of PGC-1α. AU - Ringholm,Stine, AU - Olesen,Jesper, AU - Pedersen,Jesper Thorhauge, AU - Brandt,Christina Tingbjerg, AU - Halling,Jens Frey, AU - Hellsten,Ylva, AU - Prats,Clara, AU - Pilegaard,Henriette, Y1 - 2013/08/29/ PY - 2013/04/09/received PY - 2013/07/26/revised PY - 2013/08/21/accepted PY - 2013/9/3/entrez PY - 2013/9/3/pubmed PY - 2014/6/3/medline KW - AMP-activated protein kinase KW - AMPK KW - Aging KW - CD31 KW - COX KW - CS KW - Citrate synthase KW - Cluster of differentiation KW - Cyt c KW - Cytochrome c KW - Cytochrome c oxidase KW - EDL KW - Exercise training KW - Extensor digitorum longus KW - GAPDH KW - Glyceraldehyde 3-phosphate dehydrogenase KW - Mitochondrial DNA KW - Oxidative capacity KW - PDH KW - PGC-1α KW - Peroxisome proliferator-activated receptor-γ coactivator-1α KW - Pyruvate dehydrogenase KW - Resveratrol KW - SIRT1 KW - Sirtuin 1 KW - VEGF KW - Vascular endothelial growth factor KW - mtDNA SP - 1311 EP - 8 JF - Experimental gerontology JO - Exp. Gerontol. VL - 48 IS - 11 N2 - BACKGROUND: The present study tested the hypothesis that lifelong resveratrol (RSV) supplementation counteracts an age-associated decrease in skeletal muscle oxidative capacity through peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and that RSV combined with lifelong exercise training (EX) exerts additive effects through PGC-1α in mice. METHODS: 3 month old PGC-1α whole body knockout (KO) and wild type (WT) littermate mice were placed in cages with or without running wheel and fed either standard chow or standard chow with RSV supplementation (4 g/kg food) for 12 months. Young (3 months of age), sedentary mice on standard chow served as young controls. A graded running performance test and a glucose tolerance test were performed 2 and 1 week, respectively, before euthanization where quadriceps and extensor digitorum longus (EDL) muscles were removed. RESULTS: In PGC-1α KO mice, quadriceps citrate synthase (CS) activity, mitochondrial (mt)DNA content as well as pyruvate dehydrogenase (PDH)-E1α, cytochrome (Cyt) c and vascular endothelial growth factor (VEGF) protein content were 20-75% lower and, EDL capillary-to-fiber (C:F) ratio was 15-30% lower than in WT mice. RSV and/or EX had no effect on the C:F ratio in EDL. CS activity (P=0.063) and mtDNA content (P=0.013) decreased with age in WT mice, and CS activity, mtDNA content, PDH-E1α protein and VEGF protein increased ~1.5-1.8-fold with lifelong EX in WT, but not in PGC-1α KO mice, while RSV alone had no significant effect on these proteins. CONCLUSION: Lifelong EX increased activity/content of oxidative proteins, mtDNA and angiogenic proteins in skeletal muscle through PGC-1α, while RSV supplementation alone had no effect. Combining lifelong EX and RSV supplementation had no additional effect on skeletal muscle oxidative and angiogenic proteins. SN - 1873-6815 UR - https://www.unboundmedicine.com/medline/citation/23994519/Effect_of_lifelong_resveratrol_supplementation_and_exercise_training_on_skeletal_muscle_oxidative_capacity_in_aging_mice L2 - https://linkinghub.elsevier.com/retrieve/pii/S0531-5565(13)00275-1 DB - PRIME DP - Unbound Medicine ER -