The most common intrinsic reason for sinus node dysfunction (SND) is ageing. Recent studies showed Scn5a gene mutation, which encoding Nav1.5, is also related with SND. However, it is unknown if the combination of Scn5a deficiency and ageing would induce more severe SND than single effects alone. Moreover, the exact mechanism for SND is unclear. In the present study, we hypothesized that the combined condition could lead to more severe SND through fibrosis and ion channel remodelling. Mice were divided into 4 groups: young WT, young Scn5a gene disruption mice (Scn5a+/-)(1), old WT and old Scn5a+/-. Sinus node function was characterised by measuring RR interval and sino-atrial conduction time in isolated SN preparations. Fibrosis was studied by immunohistology. Protein and mRNA expression was studied using immunohistochemistry and quantitative PCR (qPCR), respectively. Computer simulations of the electrophysiological functions of SN cells were performed. The two-way ANOVA was used for data analysis. Both ageing and Scn5a gene disruption led to declined SN function with prolonged RR interval and sino-atrial conduction time, which were even prolonged in combined ageing and Scn5a gene disruption condition. In parallel with the deteriorated sinus node function, collagen and fibroblast were increased in sinus node by either ageing or Scn5a gene disruption and to higher extent in the combined condition. TGF-β and vimentin were observed to be up-regulated by either single effect and at even higher level in the combined condition. A strong correlation between Nav1.5 gene expression decrement and TGF-β up-regulation indicates fibrosis might be related with Nav1.5 gene expression level. Dramatic increment of gene expression of TGF-β in human myocytes with treatment of flecainide further confirmed the correlation. Ion channel remodelling was studied with altered transcriptional profile. Wide range of ion channel expression down-regulation was observed in relation with ageing but not with Scn5a deficiency. Based on the data, we did computer simulation of sinus node function and obtained the similar results as experimental data. Both ageing and Scn5a deficiency can induce SND. More severe SND is developed in combined condition of ageing and Scn5a deficiency. Ageing contributes to Scn5a deficiency induced SND by ion channel remodelling and additional fibrotic process.