Sudden cardiac death accounts for 70,000 deaths in the United Kingdom and 250.000 in the United States annually. In a significant proportion the aetiology remains obscure, however recent reports implicate metabolic dysfunction as a causative factor. Metabolic dysfunction secondary to PGC-1β-/- ablation in mice has been shown to increase the incidence of lethal ventricular arrhythmias (Gurung et al. 2011). As metabolic dysfunction progresses with advancing age, we investigated interactions between ageing and mitochondrial dysfunction, upon action potential conduction characteristics as a contributor to their arrhythmic phenotype. Wild type (WT) and PGC-1β-/-, C57/B6 mice (Bar Harbour Laboratories, Maine) were divided into young WT (n=5), young PGC-1β-/- (n=9), old WT (n=8) and old PGC-1β-/- (n=6) groups. Mice were weighed, anaesthetised with tribromoethanol (240mg/kg i.p.) and electrocardiogram (ECG) signals were recorded at baseline and following dobutamine challenge (0.3mg/kg i.p.). Components of the ECG waveform and relevant intervals were analysed for statistically significant differences between groups pre and post dobutamine challenge using multivariate ANOVA. Significant differences between groups then prompted further, post hoc MANOVA decomposition and Tukey HSD tests respectively. P wave duration and atrio-ventricular node (AVN) conduction appeared normal in all animals, with no significant differences between groups at baseline. All WT mice demonstrated a normal positively dromotropic response to dobutamine. However 44% of young PGC-1β-/- and 83% of old PGC-1β-/- mice exhibited a paradoxical negatively dromotropic effect with dobutamine administration (Fig. 1). A reduction in conduction velocity is a recognised mechanism of arrhythmogenesis (King et al. 2013). We therefore next assessed ECG surrogates of ventricular conduction velocity. MANOVA analysis demonstrated significant interactive effects of genotype and age on QR and QS duration, both prior to, and following dobutamine administration (F(2,23) = 4.0031, p = 0.03223 and F(2,23) = 3.7015, p = 0.04039 respectively). Post hoc ANOVA and Tukey HSD tests showed that this difference lay in the aged PGC-1β-/- mice (Table 1). The present findings implicate age-related abnormalities in AVN function and slowed conduction through the ventricular system in the PGC-1β-/- arrhythmogenic phenotype, .