Calorie restriction (CR) is considered the only non-genetic dietary intervention implemented that increases lifespan and healthspan in a variety of species. Advancing age and malnutrition are however coupled with decreases in muscle mass (sarcopenia). We have previously shown Sirtuin1 (SIRT1) to be fundamental in muscle cell survival and regeneration in the presence of apoptotic cytokine TNF-α (Saini et al., 2012). Where loss of SIRT1 has also been shown to abrogate calorie restricted induced lifespan extension (Corbi et al., 2012). We therefore aimed to understand the role of SIRT1 in ameliorating the effect of calorie restriction (low glucose) in young and aged myoblasts originally derived by our group (Sharples et al. 2011, 2012, Deane et al., 2013). Preliminary data suggests low glucose (0.056g/L) reduced morphological and biochemical (CK) differentiation versus normal glucose (4.5g/L)in both young and aged myoblasts with reductions in corresponding myoD, myogenin, IGF-I, MGF mRNA. Aged myoblasts also experienced an increased susceptibility to these parameters in the presence of low glucose. We further confirmed that resveratrol (10uM) and SIRT inhibitor (EX-527, 100nM) were able to successfully activate and suppress respectively the activity of SIRT1 (pSIRT1) in both young and aged myoblasts. Further preliminary data suggests that when we co-incubated low glucose conditions in the absence/presence of SIRT activators/inhibitors that activation of SIRT1 ameliorated the impact of low glucose on differentiation, where resveratrol administration somewhat maintained normal differentiation in low glucose conditions. Interestingly, aged cells appear more responsive to these changes vs. young cells. We hypothesise that low glucose may induce increases in pAMPK and potentially TSC2 that maybe involved in the inhibition of mTOR/Akt /p70s6k and therefore the mechanisms that underpin reductions in muscle growth and differentiation.