In Vivo Partial Reprogramming of Senescent Cells for Rejuvenation: Technology Landscape and Roadmap

This study aims to systematically review the current landscape and future roadmap of partial reprogramming–based rejuvenation biotechnology, which seeks to revert senescent and aged cells in vivo toward a younger functional state while preserving cellular identity. Recent advances in the field have demonstrated promising preclinical potential through diverse approaches, including epigenetic resetting via transient expression of OSK/OSKM transcription factors, selective reprogramming using senescence-associated promoters (such as p16), CRISPRa-based regulation of youthful gene programs, and chemical partial reprogramming strategies. In this research, these technologies are structured and organized according to delivery modalities (AAV, LNP-mRNA, and non-viral platforms), major safety considerations (tumorigenesis risk, loss of cellular identity, immune activation), and standardized evaluation biomarkers (epigenetic clocks, senescence markers, and functional endpoints). Furthermore, the study outlines disease-first translational pathways and a mid-to-long-term development roadmap, providing a foundational framework for the advancement of in vivo rejuvenation technologies as a next-generation platform for aging-related disease intervention and healthspan extension research.