Unveiling the importance of SIRT5 for cardiac health and disease in an era of increasing longevity

As the world’s population ages, strategies to promote healthy longevity are critical. SIRT5, belonging to the sirtuin family, plays a key role in regulating cellular metabolism and mitochondrial homeostasis by removing post-translational modifications such as succinylation, malonylation, and glutarylisation from lysine residues of proteins. Herein, we discuss the multifunctionality of SIRT5, its impact on heart function, and its involvement as a target in geroscience for the pathogenesis of cardiovascular diseases, including heart failure, diabetic cardiomyopathy, cardiac hypertrophy, and ischemia-reperfusion injury. Research indicates that SIRT5 modulates metabolic pathways, oxidative stress response, and apoptosis, making it a potential therapeutic target for extending the health span and lifespan. However, its role is complex and context-dependent, exhibiting protective and harmful effects in various pathological conditions.