• piR-000699 is upregulated in aging cardiomyocytes under hypoxia/reoxygenation, promoting ferroptosis.
• SLC39A14 is identified as a direct target of piR-000699, mediating ferroptosis in aging myocardial I/R injury.
• Ferroptosis is a key cell death pathway in aging myocardial I/R injury, both in vivo and in vitro.
• Targeting piR-000699/SLC39A14 axis may offer a novel therapeutic strategy for aged myocardial I/R injury.