The epigenetic rejuvenation promise: Partial reprogramming as a therapeutic strategy for aging and disease.

Yuan-Yuan Li, Franklin R Tay

State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of General Dentistry, Xiamen University Affiliated Chenggong Hospital, The 73rd Army Hospital of Chinese PLA, Xiamen, Fujian 361001, China. Electronic address: [email protected] Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of General Dentistry, Xiamen University Affiliated Chenggong Hospital, The 73rd Army Hospital of Chinese PLA, Xiamen, Fujian 361001, China. Electronic address: [email protected]. · pubmed

Paper

Abstract

Reprogramming of somatic cells into induced pluripotent stem cells through the introduction of transcription factors Oct3/4, Sox2, Klf4, and c-Myc (OSKM) represents a landmark advance in regenerative biology. Building on this foundation, partial reprogramming can help reset epigenetic age. It further opens opportunities to treat degenerative diseases without the tumorigenic risks associated with full pluripotency. The review advances the field in three ways: it links lineage-preserving partial reprogramming to quantifiable rejuvenation endpoints; defines mesenchymal drift as an age- and disease-associated trajectory amenable to reversal; and maps strategies beyond OSKM, including small-molecule programs and CRISPR-based control circuits. Convergent phenotypes are surveyed in nervous, metabolic, musculoskeletal, and craniofacial systems, with emphasis on improved tissue repair and regeneration. A translational checklist is proposed that emphasizes schedule, delivery, and safety pharmacology to guide rigorous preclinical studies and de-risk early clinical entry points for partial reprogramming therapies.

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Research summary

The paper claims that partial reprogramming can reset epigenetic age and improve tissue repair and regeneration. This research is relevant as it addresses the underlying mechanisms of aging and proposes therapeutic strategies aimed at rejuvenation and the treatment of age-related diseases.

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