Introduction: The Senescence-Accelerated Mouse Prone (SAMP8) and its control strain SAM Resistant (SAMR1) have been established as an experimental model to study age-associated vascular dysfunction (1), but scarcely used in epigenetic studies. The small non-coding RNA molecules microRNAs (miRNAs) can repress gene expression post-transcriptionally, and are being widely studied as potential biomarkers and therapeutic drugs in cardiovascular diseases. Aims: We examine the suitableness of SAMR1/SAMP8 as a physiological model to study age-related miRNA expression after inducing an acute myocardial infarction (AMI), based on the miRNA expression profile in AMI previously described in literature (2,3). We also determine the optimal time after the AMI to measure circulating miRNA levels. Methods: Six-month old SAMR1 and SAMP8 (n = 6 per group) underwent AMI by ligation of the left anterior descending coronary artery and sham surgery. All interventions were performed under full anesthesia induced by inhalation of 5% isoflurane, and then maintained in 2% isoflurane. Animals were euthanized at different times (1h, 4h and 24h) and heart and blood were collected. AMI was confirmed by immediate discoloration of the left ventricle upon ligation, by ST segment elevation in the electrocardiogram (ECG), and by Triphenyltetrazolium chloride (TTC) staining of the non-ischemic areas of heart sections. Total RNA was obtained from serum (3) using miRNeasy Serum/Plasma Advanced Kit (Qiagen). Circulating miRNA considered as AMI biomarkers, miR-1, miR-133, miR-208 and miR-499 (2) were measured by qRT-PCR. Results are shown as mean ± SEM of the relative expression (2-ΔΔCt), using U6 snRNA as endogenous control. p-values were calculated using ANOVA and statistical significance was considered when p<0.05. The investigation complies with ethical standards and was approved by the Ethics Committee for Animal Welfare of University of Valencia (2016/VSC/PEA/00135). Results: Circulating values of miR-1, miR-133, miR-208 and miR-499 were significantly increased 4 hours after AMI when compared with sham group in both SAMR1 and SAMP8. While miR-1 totally rose at 4 hours after AMI (6.46 ± 1.32, p<0.001), miR-133, miR-208 and miR-499 levels exhibited a time-dependent upregulation, being maximal at 24 hours post-AMI (p<0.001 vs. sham group). When samples from SAMR1 and SAMP8 were compared separately, the expression of all the analyzed miRNAs were lower in SAMP8 1h after AMI (p<0.05). 4h after AMI, the ageing-related miRNAs miR-1 and miR-133 were higher in SAMP8 (p<0.05), and 24h after AMI only miR-499 expression was significantly higher in SAMP8 (p <0.05). Conclusions: The serum levels of the four miRNAs mimicked the results obtained in humans and other studies performed in animals. With the combined use of the two strains, SAMR1 and SAMP8, the effect of ageing on miRNA expression after an AMI was preferably confirmed at 4 hours after AMI. Therefore, this study proposes the SAMR1/SAMP8 mice as a suitable model to study the effects of AMI and ageing in circulating miRNA expression.