Mesenchymal Stem Cells Senescence: Mechanism and Rejuvenation Interventions

Aging has become one of the most significant challenges and burdens on public health and healthcare systems worldwide. However, it is possible to slow down the aging process through various interventions. Mesenchymal stromal/stem cells (MSCs) have emerged as one of the most promising therapeutic agents for combating aging and treating various age-related chronic medical conditions. This is primarily due to their well-known cellular plasticity and potent multipotency, which enable them to promote tissue repair and regeneration, as well as address inflammatory conditions. Remarkably, the high quality and functional activity of MSCs are negatively affected by cellular senescence, particularly in both healthy-aging MSCs and replicative senescent MSCs. This is a critical issue when considering the provision of "personalized" or "universal" clinical-grade products. Therefore, this review aims to summarize the biological properties, immunomodulatory dysfunction, and underlying mechanisms of senescent MSCs. Additionally, it discusses the current promising techniques published for rejuvenating senescent MSCs and optimizing their therapeutic potential.