Fewer androgen receptors in muscle with age leads to less Wnt5a expression and that leads to less muscle - one explanation for muscle loss with age? This study was in rats. Abstract:
We sought to determine whether age-related gastrocnemius muscle mass loss was associated with parallel decrements in androgen receptor (AR) or select Wnt signaling markers. To test this hypothesis, serum free and total testosterone (TEST) as well as gastrocnemius AR and Wnt signaling markers were analyzed in male Fischer 344 rats that were 3/6/12/18 and 24 months (mo) old (n=9 per group). Free and total TEST were greatest in 6 mo rats, and AR protein and Wnt5 protein levels linearly declined with aging. There were associations between Wnt5 protein levels and relative gastrocnemius mass (r=0.395, p=0.007) as well as AR and Wnt5 protein levels (r=0.670, p<0.001). We next tested the hypothesis that Wnt5 affects muscle fiber size by treating C2C12-derived myotubes lower (75 ng/mL) and higher (150 ng/mL) concentrations of recombinant Wnt5a protein. Both treatments increased myotube size (p<0.05) suggesting this ligand may affect muscle fiber size in vivo. We next tested if Wnt5a protein levels were androgen-modulated by examining 10 mo old male Fischer 344 rats (n=10-11 per group) that were orchiectomized and treated with testosterone-enanthate (TEST-E), trenbolone enanthate (TREN), a non-aromatizable synthetic testosterone analogue, or a vehicle (ORX only) for 4 weeks. Interestingly, TEST-E and TREN treatments increased Wnt5a protein in the androgen-sensitive levator ani/bulbocavernosus (LABC) muscle compared ORX only (p<0.05). To summarize, aromatizable and non-aromatizable androgens increase Wnt5a protein expression in skeletal muscle, age-related decrements in muscle AR may contribute Wnt5a protein decrements, and our in vitro data imply this mechanism may contribute to age-related muscle loss.
No comments:
Post a Comment