Modulation of overload-induced inflammation by aging and anabolic steroid administration

Abstract

Aging can alter the skeletal muscle growth response induced by overload. The initiation of overload induces muscle extracellular matrix expansion, increased cellularity, and inflammatory gene expression, which are all related to processes important for myofiber growth. These remodeling processes are also biological targets of testosterone. It is not certain how aging affects the inflammatory response to functional overload and whether anabolic steroid administration can alter this response. The effect of anabolic steroid administration on inflammatory processes during functional overload is not known. The purpose of this study was to determine if age altered the skeletal muscle inflammatory response at the onset of functional overload and whether anabolic steroid administration would modulate this response in young or older animals. Five-month and 25 month F344 × BRN rats were given nandrolone decanoate (ND) (6 mg/kg bw/wk) or sham injections for 3 weeks, and then the soleus muscle was overloaded (OV) for 3 days by synergist ablation. ND alone induced a 230% increase in ED1 + cells in 5 month muscle. Three days of OV had no effect on ED1 + cell number at either age. OV combined with ND induced a 90% increase in ED2 + cells in 5 month muscle, while there was no effect of either treatment alone at this age. In 25 month muscle, OV induced a 40% increase in ED2 + cells. Regardless of age, OV induced muscle TNF-α mRNA expression (300%) and IL-6 mRNA expression (900%). ND attenuated OV-induced IL-6 mRNA but not TNF-α expression in both age groups. The overload induction of IL-1β mRNA was 3-fold greater in 25 month muscle (1400%), compared to 5 month muscle (400%). ND administration ablated the overload IL-1β mRNA induction in 25 month muscle. Anabolic steroid administration can suppress inflammatory cytokine gene expression at the onset of overload and this effect is age dependent.