GeroScience

, Volume 39, Issue 2, pp 175–186 | Cite as

Influence of Nrf2 activators on subcellular skeletal muscle protein and DNA synthesis rates after 6 weeks of milk protein feeding in older adults

  • Adam R. Konopka
  • Jaime L. Laurin
  • Robert V. Musci
  • Christopher A. Wolff
  • Justin J. Reid
  • Laurie M. Biela
  • Qian Zhang
  • Fredrick F. PeelorIII
  • Christopher L. Melby
  • Karyn L. Hamilton
  • Benjamin F. Miller
Original Article

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.

Keywords

Sarcopenia Proteostasis Oxidative stress Inflammation Anabolic resistance 

Supplementary material

11357_2017_9968_MOESM1_ESM.pdf (28 kb)
Online Resource 1Plasma 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)
11357_2017_9968_MOESM2_ESM.pdf (36 kb)
Online Resource 2Sexual 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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Copyright information

© American Aging Association 2017

Authors and Affiliations

  • Adam R. Konopka
    • 1
  • Jaime L. Laurin
    • 1
  • Robert V. Musci
    • 1
  • Christopher A. Wolff
    • 1
  • Justin J. Reid
    • 1
  • Laurie M. Biela
    • 1
  • Qian Zhang
    • 1
  • Fredrick F. PeelorIII
    • 1
  • Christopher L. Melby
    • 1
  • Karyn L. Hamilton
    • 1
  • Benjamin F. Miller
    • 1
  1. 1.Department of Health and Exercise ScienceColorado State UniversityFort CollinsUSA

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