Stem Cell and Stem Cell-Derived Extracellular Vesicles: Therapeutic Potential and Mechanistic Insights in Anti-Aging.

Aging is driven by interconnected molecular and cellular processes (senescence, inflammation, proteostasis decline, mitochondrial dysfunction) that reduce tissue repair and organismal resilience, resulting in an increased prevalence of chronic degenerative conditions. Accordingly, the development of strategies to prevent, delay, or mitigate multiple age-related diseases is imperative. Embryonic stem cells (ESCs) and other pluripotent stem cells (PSCs) offer substantial therapeutic potential owing to their self-renewal and cellular plasticity, but their direct clinical use is limited by concerns of immunogenicity, tumorigenicity, and ethical constraints. ESC- and PSC-derived extracellular vesicles (ESC-EVs/PSC-EVs) have emerged as promising alternatives that may capture many of the regenerative and modulatory benefits of their parent cells while reducing associated risks. Cumulative evidence shows that EVs from young or stem-like cells mainly produce rejuvenating effects across tissues and molecular pathways. Here we summarize key biological features of stem cells and their EVs, outline mechanisms by which EVs impact aging hallmarks, and assess preclinical and early clinical findings on stem cell and EVs interventions for aging and age-related diseases. Careful optimization of EVs production, standardized characterization, and thorough safety and efficacy testing in diverse disease models and clinical contexts are essential to translate PSC-EVs approaches into viable therapies.