Abstract
In older adults, chronic oxidative and inflammatory stresses are associated with an impaired increase in skeletal muscle protein synthesis after acute anabolic stimuli. Conjugated linoleic acid (CLA) and Protandim have been shown to activate nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor for the antioxidant response element and anti-inflammatory pathways. This study tested the hypothesis that compared to a placebo control (CON), CLA and Protandim would increase skeletal muscle subcellular protein (myofibrillar, mitochondrial, cytoplasmic) and DNA synthesis in older adults after 6 weeks of milk protein feeding. CLA decreased oxidative stress and skeletal muscle oxidative damage with a trend to increase messenger RNA (mRNA) expression of a Nrf2 target, NAD(P)H dehydrogenase quinone 1 (NQO1). However, CLA did not influence other Nrf2 targets (heme oxygenase-1 (HO-1), glutathione peroxidase 1 (Gpx1)) or protein or DNA synthesis. Conversely, Protandim increased HO-1 protein content but not the mRNA expression of downstream Nrf2 targets, oxidative stress, or skeletal muscle oxidative damage. Rates of myofibrillar protein synthesis were maintained despite lower mitochondrial and cytoplasmic protein syntheses after Protandim versus CON. Similarly, DNA synthesis was non-significantly lower after Protandim compared to CON. After Protandim, the ratio of protein to DNA synthesis tended to be greater in the myofibrillar fraction and maintained in the mitochondrial and cytoplasmic fractions, emphasizing the importance of measuring both protein and DNA synthesis to gain insight into proteostasis. Overall, these data suggest that Protandim may enhance proteostatic mechanisms of skeletal muscle contractile proteins after 6 weeks of milk protein feeding in older adults.
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Acknowledgements
This work was supported by the Dairy Research Institute and LifeVantage, Inc. (to KLH and BFM). The authors would like to thank the participants for their time and commitment to this study. We are grateful for the assistance of Gary Luckasen, M.D., and Jon Matthews, M.D., and their associates for providing medical oversight. We would also like to acknowledge the technical assistance provided by Gaia Bublitz, Kim Cox-York, PhD., and the Metabolomics and Proteomics Facility at Colorado State University. Analysis for C-reactive protein was performed at the University of Colorado Hospital Clinical and Translational Research Centers, which is a service within the Colorado Clinical and Translational Sciences Institute (CCTSI), supported in part by NIH/NCATS Colorado CTSI Grant Number UL1 TR001082.
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This study was approved by the Institutional Review Board at Colorado State University (13-4191H). Prior to beginning participation, each participant was informed of the study design, potential risk, and benefits and provided written consent.
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Karyn L. Hamilton and Benjamin F. Miller are co-senior authors.
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Online Resource 1
Plasma concentration of C18:2 isomers (A) and cis-9, trans-11 and trans-10, cis-12 isomers (B). Cis-9, trans-11 and trans-10, cis-12 isomers co-eluted at the same retention time. Therefore, the overlapping CLA isomers were calculated using both standard curves and an average was taken. Undetectable levels were observed in CON and pre CLA. Therefore, individual data are presented. Detectable levels were observed in each participant post CLA. (PDF 28 kb)
Online Resource 2
Sexual dimorphism in the ratio of myofibrillar protein to DNA synthesis after 6 weeks of milk protein feeding with control (CON; n=4 Men, n=8 Women) and Protandim (n=5 men, n=10 women). Data presented as mean ± SEM. *P<0.05 vs. Protandim women; P=0.06 vs. CON Men. (PDF 35 kb)
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Konopka, A.R., Laurin, J.L., Musci, R.V. et al. Influence of Nrf2 activators on subcellular skeletal muscle protein and DNA synthesis rates after 6 weeks of milk protein feeding in older adults. GeroScience 39, 175–186 (2017). https://doi.org/10.1007/s11357-017-9968-8
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DOI: https://doi.org/10.1007/s11357-017-9968-8