Background: The size of the elderly population is continually increasing and it has been predicted that by 2035 over 25% of the Western population will be elderly (≥ 65 years of age) (Lakatta, 2002). Dysfunction of the sinoatrial (SA) node has been shown to be at its highest incidence within the elderly population. Those who suffer SA node dysfunction experience a range of symptoms including dizziness, fatigue and palpitations, clinically observed as rhythm disturbances, sinus pauses and arrhythmias; the patients are classed as suffering ‘sick sinus syndrome’ and without clinical intervention are at high risk of sudden death (Ross & Kenny, 2000). Effective long-term treatment employs catheter ablation and/or implantation of an artificial pacemaker. However, elderly patients are frequently unfit for surgery, and those over 70 years of age with sick sinus syndrome experience minimal improvement in their cardiac function (Fleischmann et al. 2006). My hypothesis was to prove the existence of an age-dependent decrease in the protein expression of the gap junction connexin43 (Cx43) and the channel Cav1.2, accompanying an associated decline in pacemaker function. Furthermore, I hypothesised that the stress activated c-jun N-terminal kinase (JNK), an intracellular signalling mediator, is implicated in the reduced expression of these proteins. Methods and Results: The SA node region was dissected from rodents between birth and the end of their lifespan. My data showed that the rodent intrinsic heart rate decreased with age to 70-80% of the rate observed in the young animal, paralleling a comparable decrease reported in humans by Opthof (2000). Protein analysis by immunofluorescence and Western blot showed a decline in expression of the Cav1.2 channel within the SA node during ageing, functionally exhibited as an increased sensitivity of the SA node to nifedipine (a Cav1.2 channel blocker), resulting in an age-dependent decrease in the EC50 for complete abolition of SA node activity (Jones et al. 2007). Analysis of protein expression also demonstrated a substantial decline in Cx43 expression, accompanied by remodelling of expression of the remaining Cx43 protein in the aged SA node tissue. This was associated with an alteration in the conduction properties within the node and postulated to contribute to pacemaker degeneration with age (Jones et al. 2004). The decline of Cx43 protein within the SA node correlated with increasing levels of activated JNK in the heart implicating JNK in the regulation of Cx43 protein and SA node remodelling during progressive ageing (n=5 per age group; ANOVA p<0.01; Linear regression y=1.0305X-0.3484; R2=0.96). Conclusion: This is the first evidence that the JNK-mediated pathway is a signalling mechanism implicated in cardiac ageing, associating with the age-dependent decline of Cx43 and Cav1.2 channel with the SA node. By further defining the degenerative changes limiting the cardiac pacemaker function in the elderly and the mechanisms responsible for these it may prove possible to limit the progression of SAN dysfunction in the elderly.