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One particular challenge facing translation is the existence of demographic and clinical factors that influence the pathophysiology of ischaemia\u2013reperfusion injury of the heart and the effects of treatments aimed at preventing it. Among these factors, age and sex are prominent and have a recognised role in the susceptibility and outcome of ischaemic heart disease. Remarkably, some of the most powerful cardioprotective strategies proven to be effective in young animals become ineffective during ageing. This article reviews the mechanisms and implications of the modulatory effects of ageing and sex on myocardial ischaemia\u2013reperfusion injury and their potential effects on cardioprotective interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. 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