Endurance performance relies upon efficient production of ATP in skeletal muscle via mitochondrial oxidative phosphorylation. As such, skeletal muscle mitochondrial biogenesis is a predominant mechanism by which endurance training improves performance. From a molecular perspective, various molecules interact to regulate mitochondrial content and function in skeletal muscle. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, has been proposed to play an intimate role in mitochondrial biogenesis and is sensitive to metabolic fluctuations invoked by endurance exercise. However, despite considerable research attention, relatively little is known regarding exercise-induced adaption mediated by SIRT1 in skeletal muscle. Therefore, to determine SIRT1-deactylase dependent signalling in skeletal muscle, SIRT1 muscle-specific knockout mice (mKO) and control wild-type (WT) littermates underwent acute treadmill running in the fasted state (60 minutes at intervals of 5-25 m/min @ 10° gradient). Following endurance performance, mice were sacrificed immediately post exercise and one and three hours-post exercise (n=6/group). Immunoblotting techniques were used to determine protein content and post-translational modification of the purported SIRT1 targets p53, CREB and AMPK. Despite loss of SIRT1 activity in the mKO group, we observed comparable phosphorylation of p53, CREB and AMPK post exercise in both mKO and WT mice, suggesting that factors in addition to SIRT1 regulate the phosphorylation and presumed activity of these targets following endurance exercise.