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Rejuvenation Potential of Developmental Genes Downregulated in Aging

Byungkuk Min1, Juhyeon Nam1, Minseo Choi1,2

  • 1Center for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.

International Journal of Stem Cells
|June 9, 2026
PubMed

Insights

Researchers identified four novel rejuvenation induction factors (RIFs) that reverse cellular aging markers without the oncogenic risks associated with Yamanaka factors, offering a safer strategy for age-related disease therapies.

Area of Science:

  • Cellular Biology
  • Genetics
  • Aging Research

Background:

  • Partial reprogramming using Yamanaka factors can reverse cellular aging but carries oncogenic risks, hindering clinical applications.
  • Identifying safer alternatives for cellular rejuvenation is crucial for therapeutic development.

Purpose of the Study:

  • To discover novel, safer rejuvenation induction factors (RIFs) that can reverse cellular aging without inducing pluripotency or oncogenic transformation.
  • To identify molecular targets that counteract age-related transcriptional changes.

Main Methods:

  • Integrated five aging datasets with single-cell transcriptomics from mouse preimplantation embryos.
  • Compared gene expression patterns between aging and early development.
  • Identified genes upregulated during development and downregulated during aging, and refined this list using Yamanaka factor reprogramming data.

Main Results:

  • Isolated four RIFs involved in ribosome biogenesis, mitochondrial import, translational regulation, and serine metabolism.
  • Demonstrated that these RIFs reduce senescence markers in aged fibroblasts.
  • Showed RIFs restore age-associated gene expression patterns without activating pluripotency pathways.

Conclusions:

  • The identified RIFs represent a potentially safer approach to cellular rejuvenation than Yamanaka factors.
  • These factors modulate age-associated developmental pathways, offering a new therapeutic avenue for aging.
  • RIFs avoid the oncogenic risks linked to Yamanaka factors, paving the way for clinical translation.
Keywords:
Age-associated genesDevelopmental gene expressionPartial reprogrammingPreimplantation embryosRegenerative medicineSingle-cell transcriptomics

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