# Urolithin A Alleviates Doxorubicin-Induced Senescence in Mesenchymal Stem Cells

## TL;DR

Urolithin A reduces signs of aging in stem cells damaged by a chemotherapy drug, potentially improving regenerative treatments.

## Contribution

Urolithin A is shown to be a senomorphic agent that modulates senescence in MSCs without being toxic.

## Key findings

- Urolithin A suppresses the SASP by reducing pro-inflammatory mediators like MCP1, PAI2, and IL1B.
- Urolithin A reverses the decline in H3K9me3 levels caused by Doxorubicin treatment.
- Urolithin A may enhance regenerative medicine when combined with senolytic therapies.

## 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.