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.

Short-term weight loss reverses obesity-induced microvascular endothelial dysfunction

“…Funding information This work was supported by the National Institutes of Health (NIH) Grants R01-AT-006526, R01-AG047879, R01-AG038747, and R01-NS056218, the Geroscience Training Program in Oklahoma (NIH Grant T32-AG-052363), the Oklahoma Nathan Shock Center (NIH Grant 3-P30-AG050911-02S1), the Oklahoma Shared Clinical and Translational Resources (NIH Grant U54-GM-104938), the Oklahoma Center for the Advancement of Science and Technology (HR17-070), the College of Medicine Alumni Association, the Presbyterian Health Foundation, and the EU-funded grant EFOP-3.6.1-16-2016-00008. The paper was published as part of the BTranslational Geroscience^initiative of the Journal of the American Aging Association (Ashpole et al 2017;Bennis et al 2017;Callisaya et al 2017;Csiszar et al 2017;Deepa et al 2017;Grimmig et al 2017;Hancock et al 2017;Kane et al 2017;Kim et al 2017;Konopka et al 2017;Liu et al 2017;Meschiari et al 2017;Perrott et al 2017;Podlutsky et al 2017;Shobin et al 2017;Sierra and Kohanski 2017;Tarantini et al 2017a;Tarantini et al 2017b;Tenk et al 2017;Tucsek et al 2017;Ungvari et al 2017a, b ;Urfer et al 2017a, b).…”

The concept of skeletal muscle memory: Evidence from animal and human studies

“…The process of myonuclear addition to a muscle fibre requires satellite cell activation, replication and differentiation, during which DNA synthesis occurs 11 . Stable isotope tracer approaches have been successfully applied to label nucleotide base pairs (ie, pyridine deoxyribonucleotides) and measure DNA synthesis rates in the blood and muscle tissue of rodents and humans 17‐111 . Robinson et al 18 were the first to orally administer deuterated water ( 2 H 2 O) and assess muscle DNA synthesis rates over several weeks in humans.…”

Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation

“…Disclaimer The data were presented at the 14th International Symposium on Neurobiology and Neuroendocrinology of Aging (July 15-20, 2018, Bregenz, Austria). This paper is part of a special collection of papers published in GeroScience on the oxidation-inflammation theory of aging (Tucsek et al 2017;Konopka et al 2017;Aiello et al 2017;Blodgett et al 2017;Deepa et al 2017;Jackson et al 2017;Lee et al 2017;Meschiari et al 2017;Nikolich-Zugich and van Lier 2017;Perrott et al 2017;Rais et al 2017;Shobin et al 2017;Souquette et al 2017).…”