2. Academic Validation
  3. Urolithin A Alleviates Doxorubicin-Induced Senescence in Mesenchymal Stem Cells

Urolithin A Alleviates Doxorubicin-Induced Senescence in Mesenchymal Stem Cells

  • Int J Mol Sci. 2025 Oct 22;26(21):10257. doi: 10.3390/ijms262110257.
Alexander Kalinin 1 2,  Ekaterina Zubkova 1,  Mikhail Menshikov 1,  Yelena Parfyonova 1 2
Affiliations

Affiliations

  • 1 National Medical Research Centre of Cardiology Named After Academician E.I. Chazov, Moscow 121552, Russia.
  • 2 Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow 119991, Russia.
PMID: 41226300 DOI: 10.3390/ijms262110257
Abstract

The accumulation of senescent cells, characterized by a pro-inflammatory secretory phenotype (SASP), metabolic dysfunction, and irreversible cell cycle arrest, is a driving force behind numerous age-related pathologies and directly undermines the therapeutic potential of mesenchymal stem cells (MSCs). In this study, we explore the senotherapeutic potential of urolithin A, a renowned antioxidant compound, in human adipose-derived MSCs (AD-hMSCs). Our findings reveal that urolithin A is non-cytotoxic to senescent AD-hMSCs and significantly suppresses the SASP by reducing the secretion of key pro-inflammatory mediators, including MCP1, PAI2, and IL1B. In addition, it was demonstrated that urolithin A was capable of reversing the decline in H3K9me3 levels induced by Doxorubicin treatment, restoring them to levels observed in untreated cells. The results of this study suggest that urolithin A functions as a senomorphic agent, capable of modulating cellular senescence. Moreover, its combination with senolytic therapies has the potential to yield novel and effective treatment strategies for regenerative medicine.

Keywords

aging; autophagy; cellular senescence; doxorubicin; mesenchymal stem cells; senotherapeutics.

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