RESUMEN
Liver regeneration is a remarkably complex phenomenon conserved across all vertebrates, enabling the restoration of lost liver mass in a matter of days. Unfortunately, extensive damage to the liver may compromise this process, often leading to the death of affected individuals. Ischemia/reperfusion injury (IRI) is a common source of damage preceding regeneration, often present during liver transplantation, resection, trauma, or hemorrhagic shock. Increased oxidative stress and mitochondrial dysfunction are key hallmarks of IRI, which can jeopardize the liver's ability to regenerate. Therefore, a better understanding of both liver regeneration and IRI is of important clinical significance. In the current review, we discuss the potential role of sestrin 2 (SESN2), a novel anti-aging protein, in liver regeneration and ischemia/reperfusion preceding regeneration. We highlight its beneficial role in protecting cells from mitochondrial dysfunction and oxidative stress as key aspects of its involvement in liver regeneration. Additionally, we describe how its ability to promote the expression of Nrf2 bears significant importance in this context. Finally, we focus on a potential novel link between SESN2, mitohormesis and ischemic preconditioning, which could explain some of the protective effects of preconditioning.