6 Weeks Of Nrf2-activator And Protein Supplementation Improves Myofibrillar Proteostasis In Men.

Abstract

The age-related loss of muscle mass and function are key contributors to the decline in healthspan. Maintenance of protein homeostasis (proteostasis) is critical to maintain muscle quality and function during advancing age. We have previously shown that interventions that slow aging increase the ratio of skeletal muscle protein to DNA synthesis, which we believe are indicative of improved proteostatic mechanisms. Oxidative stress and inflammation blunt the anabolic response to protein feeding, thus supplementation with a nuclear factor, erythroid 2 like 2 (Nrf2) activator could restore the anabolic response to protein feeding in older adults. PURPOSE: To test the hypothesis that supplementing with a Nrf2 activator alongside protein feeding would increase muscle subcellular protein synthesis in skeletal muscle of older adults. METHODS: In a 6-week double-blind study, older adults (n=46, 60-77 years old) were randomized to protein supplementation with placebo (CON) or one of the Nrf2 activators conjugated linoleic acid (CLA) or Protandim (PTD). We used deuterium-labeled water to measure DNA synthesis and protein synthesis in myofibrillar, mitochondrial, and cytosolic enriched fractions of skeletal muscle. RESULTS: PTD maintained myofibrillar protein synthesis while mitochondrial and cytoplasmic protein synthesis decreased (p<0.05). There was no change in DNA synthesis with PTD or CLA supplementation compared to CON. PTD tended to increase the myofibrillar protein: DNA synthesis ratio compared to CON (PTD 5.55 ± 1.364 vs CON 4.691 ± 0.749; p=0.07). Increased myofibrillar protein:DNA synthesis after PTD was more apparent in men. CONCLUSIONS: We report that protein supplementation with a Nrf2 activator tended to increase myofibrillar protein:DNA synthesis ratio which was more profound in men versus women. Given that protein:DNA synthesis is a measure of proteostasis, our results demonstrate that protein supplementation with a Nrf2 activator to diminish oxidative stress and inflammation improves proteostasis in older adult men. Additional studies are warranted to determine if maintaining myofibrillar proteostasis with PTD or more potent Nrf2 activators may help maintain muscle mass and function with age in both men and women. Supported by the National Dairy Council.