Replacement as an aging intervention.

Substantial progress in aging research continues to deepen our understanding of the fundamental mechanisms of aging, yet there is a lack of interventions conclusively shown to attenuate the processes of aging in humans. By contrast, replacement interventions such as joint replacements, pacemaker devices and transplant therapies have a long history of restoring function in injury or disease contexts. Here, we consider biological and synthetic replacement-based strategies as aging interventions. We discuss innovations in tissue engineering, such as the use of scaffolds or bioprinting to generate functional tissues, methods for enhancing donor-recipient compatibility through genetic engineering and recent progress in both cell therapies and xenotransplantation strategies. We explore synthetic approaches including prostheses, external devices and brain-machine interfaces. Additionally, we evaluate the evidence from heterochronic parabiosis experiments in mice and donor-recipient age-mismatched transplants to consider whether systemic benefits could result from personalized replacement approaches. Finally, we outline key challenges and future directions required to advance replacement therapies as viable, scalable and ethical interventions for aging.