title: Influence of Nrf2 activators on subcellular skeletal muscle protein and DNA synthesis rates after 6 weeks of milk protein feeding in older adults.
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.
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA. Adam.Konopka@colostate.edu.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Konopka
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Laurin
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Musci
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Wolff
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Reid
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Laurie M
authors.initials: LM
authors.lastname: Biela
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Fredrick F
authors.initials: FF
authors.lastname: Peelor
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Melby
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Karyn L
authors.initials: KL
authors.lastname: Hamilton
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 110 Moby B Complex, Fort Collins, CO, 80523, USA.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Miller
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins / Q000627:therapeutic use*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D044243:Linoleic Acids, Conjugated; D008894:Milk Proteins; D009124:Muscle Proteins; D051267:NF-E2-Related Factor 2; C509374:Protandim; D012333:RNA, Messenger; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone)
keywords: Anabolic resistance; Inflammation; Oxidative stress; Proteostasis; Sarcopenia