Stem cell dysfunction and rejuvenation strategies in ageing: emerging advances in regenerative medicine

Ageing is a complicated phenomenon that is defined by the progressive decline in the body's functions that leads to weakened regenerative potential and greater vulnerability to various age-related diseases. There is evidence that highlights that stem cell dysfunction and exhaustion are the primary reasons for tissue degeneration that progresses with age and hence provide aid to regenerative therapeutic approaches. Stem cells have shown the ability to influence age-related cellular dysfunction in preclinical models mainly via paracrine signaling, immune modulation and tissue repair processes. Nonetheless, clinical evidence primarily confines to early-phase trials, showing inconsistent results based on cell type, delivery method and disease context. Several types of stem cells are being studied rigorously for their regenerative, immunomodulatory, and anti-ageing properties. Pre-clinical and early-phase clinical studies suggest potential benefits of stem cell-based interventions in musculoskeletal, cardiovascular and neurodegenerative disorders although effect sizes vary and long-term efficacy remains under investigation. Furthermore, emerging technologies such as tissue reprogramming, senolytics and niche modulation also contribute to improving therapeutic strategies. This review aims to provide a comprehensive overview of the existing knowledge of stem cell biology and therapies from various preclinical and clinical studies, along with rejuvenation approaches.