Anti-aging strategies and ex vivo organ rejuvenation.

Abstract

Aging is characterized by a progressive decline in physiological function, driven by interconnected molecular hallmarks that increase the risk of chronic diseases. To extend health span, interventions targeting these hallmarks, including lifestyle modifications, pharmacological agents, and genetic strategies, have been developed. Among these, partial reprogramming, the transient expression of Yamanaka factors, has emerged as a powerful approach to reverse age-related cellular damage and restore youthful epigenetic and transcriptional signatures without erasing cell identity. This perspective highlights the therapeutic possibilities arising from the convergence of partial reprogramming with the innovative technology of ex vivo machine perfusion. These platforms offer a unique opportunity to apply rejuvenation therapies directly to suboptimal donor organs outside the body before transplantation. Combining these strategies could significantly improve organ quality, expand the donor pool, enhance transplantation outcomes, and advance regenerative medicine.