Early Life Androgen Administration Attenuates Aging Related Declines in Muscle Protein Synthesis

Abstract

Purpose This study examined the acute and long-term effects of nandrolone decanoate (ND) on fractional synthetic rates (FSR). Methods Male C57BL/6 mice were randomized into ND (n = 20) or sham (n = 20) groups. ND injections (10 g·kg-1·wk-1) started at 7-month of ages and continued for 6-weeks. Ten animals from each group were randomly separated and examined 1-week following drug cessation. The remaining animals were examined at 16-months of age. Animals were injected IP with 1.5 ml of deuterated water 24-h prior to euthanasia. The kidney, liver, heart, gastrocnemius, and soleus were extracted. Samples were analyzed for deuterated alanine enrichment in the bound protein and intracellular fraction by LC-MS/MS to measure estimated FSR (fraction/day [F/D]) of mixed tissue PS. Results One-way analysis of variance, with treatment and age as fixed factors, indicated that kidney FSR was (p = 0.027) greater in ND (0.41 ± 0.02 F/D) than sham (0.36 ± 0.014F/D) and higher (p = 0.003) in young (0.42 ± 0.2 F/D) than old (0.35 ± 0.01 F/D). Liver and heart FSR were greater (p’s ≤ 0.001) in young (0.79 ± 0.06 F/D, and 0.13 ± 0.01 F/D, respectively) compared to old (0.40 ± 0.01 F/D and 0.09 ± 0.01 F/D, respectively), but not between ND and sham. Gastrocnemius FSR was (p ≤ 0.001) greater in young (0.06 ± 0.01 F/D) compared to old (0.03 ± 0.002 F/D), and greater (p = 0.006) in ND (0.05 ± 0.01 F/D) compared to sham (0.04 ± 0.003 F/D). Soleus FSR rates were greater (p = 0.050) in young (0.13 ± 0.01 F/D) compared to old (0.11 ± 0.003 F/D) but, not between ND (0.12 ± 0.01 F/D) and sham (0.12 ± 0.01 F/D). Old animals who had received ND displayed elevated FSR in the gastrocnemius (p = 0.054) and soleus (p = 0.024). Conclusions ND use in young adult animals appeared to maintain long-term elevations in FSR in muscle during aging.