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Updated: Jul 24, 2025

Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle
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Partial cellular reprogramming stably restores the stemness of senescent epidermal stem cells

Y-R Su1, S-M Gu, Y-R Liu

  • 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China. wangzhichong@gzzoc.com.

European Review for Medical and Pharmacological Sciences
|July 4, 2023
PubMed
Abstract

Insights

Partial reprogramming using OSKM factors rejuvenates senescent stem cells, restoring self-renewal and proliferation without losing cell identity. This approach shows promise for treating age-associated diseases.

Area of Science:

  • Stem cell biology
  • Aging research
  • Regenerative medicine

Background:

  • Adult stem cell senescence drives organismal aging and age-associated diseases.
  • Restoring stem cell self-renewal offers therapeutic targets for healthspan extension.
  • Partial cellular reprogramming via OSKM factors can ameliorate age-related hallmarks in somatic cells.

Purpose of the Study:

  • To investigate the effects of partial reprogramming on senescent epidermal stem cells (ESCs).
  • To determine if transient OSKM expression can restore self-renewal and youthful characteristics in aged ESCs.
  • To explore the impact of partial reprogramming on cellular identity and DNA methylation patterns.

Main Methods:

  • Senescent Integrin-α6highCD71high ESCs were treated with transient OSKM expression.
  • Self-renewal ability was assessed by secondary clone generation and proliferation assays.
  • Stem cell markers (p63, Ki67) and epidermal cell markers were analyzed.
  • DNA methylation age (eAge) and DNA methyltransferase activity were evaluated.

Main Results:

  • Partial reprogramming restored youthful self-renewal and proliferation in senescent ESCs.
  • Epithelial cellular identity was preserved post-reprogramming.
  • Rejuvenation effects were maintained for 2 weeks after OSKM withdrawal.
  • Partial reprogramming counteracted accelerated eAge in senescent ESCs, with DNMT1 playing a potential role.

Conclusions:

  • Partial reprogramming effectively rejuvenates senescent adult stem cells.
  • This method holds significant therapeutic potential for treating age-associated diseases.
  • It offers a novel strategy for reversing stem cell aging and extending healthspan.

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