Plant-derived extracellular vesicles (PDEVs) in anti-aging research: A review of biomedical characteristics and therapeutic applications.

Aging is a complex, irreversible physiological process characterized by gradual deterioration of tissue structure and function, accompanied by impaired regenerative capacity, dysregulated immune homeostasis, and increased susceptibility to chronic age-related diseases (e.g., neurodegenerative disorders, metabolic syndromes, age-related skin lesions, and inflammatory bowel disease). In recent years, plant-derived extracellular vesicles (PDEVs), the lipid bilayer membrane vesicles released by plant cells, have emerged as innovative candidates for anti-aging therapy because of their inherent biocompatibility, safety, and sustainable sourcing advantages. These nanoscale particles contain proteins, lipids, and nucleic acids. Emerging evidence from in vitro and rodent in vivo models has indicated that PDEVs can effectively delay age-related phenotypes and alleviate pathological changes through multiple mechanisms, such as scavenging reactive oxygen species to mitigate oxidative damage, regulating the immune microenvironment to suppress chronic inflammation, modulating gut microbiota composition to restore intestinal homeostasis, and promoting tissue regeneration (a core application in regenerative medicine) by activating stem cell function and repairing damaged tissues. Additionally, PDEVs offer unique potential as natural or engineered cargo-carriers for drug loading and delivery. This review outlines the biogenesis, composition, isolation, characterization, and storage strategies for PDEVs. Furthermore, we systematically summarize advances in the biological functions of PDEVs and their therapeutic applications in various age-related diseases. Finally, we discuss current challenges and future prospects for PDEVs in clinical translation. We hope this work provides valuable insights for advanced research and potential applications of PDEVs in the management of aging and age-related diseases.