Paras Ahmad, Nathan E Estrin, Anton Sculean, Richard J Miron
EVs represent promising therapeutic agents and biomarkers in aging biology, with the potential to regulate multiple hallmarks of aging concurrently. Prospective research should prioritize standardization, targeted bioengineering, and rigorous clinical validation to allow successful antiaging interventions.
BACKGROUND: Aging is a multifactorial process marked by gradual cellular dysregulation, regulated by hallmarks, including genomic instability, mitochondrial dysregulation, and chronic inflammation. Extracellular vesicles (EVs), especially exosomes, have emerged as pivotal mediators of cell-to-cell communication with potential roles in both enhancing and alleviating aging. This review aimed to synthesize existing literature on the mechanistic and therapeutic role of EVs in aging and age-associated disorders.
METHODS: A comprehensive narrative review was performed utilizing Web of Science, Scopus, and PubMed databases. Studies assessing EVs in aging, cellular senescence, regenerative biology, and age-related disorders were included. Both preclinical and clinical studies were qualitatively examined, emphasizing EV origin, molecular pathways, and treatment outcomes.
RESULTS: EVs derived from young or stem cells show strong antiaging features across multiple systems, such as the immune, musculoskeletal, cardiovascular, and nervous systems. These impacts are regulated via mitigating cellular senescence, reestablishing mitochondrial activity, restoring mitophagic and autophagic signaling, regulating inflammatory signaling, and improving tissue regeneration. Contrarily, EVs from diseases or aged cells improve pro-aging phenotypes, such as inflammation, fibrosis, and metabolic dysregulation, underscoring their context-mediated duality. Preclinical evidence consistently supports EV-mediated therapies; nonetheless, clinical translation remains restricted owing to heterogeneity in EV subpopulations, lack of standardized isolation protocols, and variability in bioactive payload.
CONCLUSION: EVs represent promising therapeutic agents and biomarkers in aging biology, with the potential to regulate multiple hallmarks of aging concurrently. Prospective research should prioritize standardization, targeted bioengineering, and rigorous clinical validation to allow successful antiaging interventions.