Nasal Mucosa‐Derived Extracellular Vesicles as a Systemic Antiaging Intervention

This study shows that nasal mucosa‐derived extracellular vesicles (nmEVs) exert systemic anti‐ageing effects in mice by restoring circadian rhythm, suppressing cellular senescence, and improving cognitive function. In aged human bone marrow mesenchymal stem cells, nmEVs reverse senescence‐associated phenotypes and reactivate core clock gene expression. Abstract Aging impairs tissue function and regenerative capacity across multiple organs. This study demonstrates that extracellular vesicles derived from human nasal mucosa (nmEVs) exert systemic antiaging effects in aged mice. Treatment with nmEVs improves cognitive performance and alters hippocampal aging signatures related to synaptic signaling and the regulation of neuroplasticity. In parallel, transcriptomic analysis of five major aging‐sensitive organs reveals that nmEVs broadly ameliorate age‐associated transcriptional changes, notably by restoring circadian rhythmicity and suppressing cellular senescence‐related pathways. At the cellular level, nmEVs alleviate senescence phenotypes in aged human bone marrow mesenchymal stem cells, restore proliferation and osteogenic capacity, and reactivate core clock gene expression. These effects are accompanied by modulation of the p53 pathway, suggesting its involvement in nmEV‐mediated rejuvenation. Importantly, lacking the need for cell isolation and ex vivo expansion, nmEVs offer a practical, age‐independent source of extracellular vesicles with high clinical accessibility. Together, these findings support the translational potential of nmEVs as a multifaceted therapeutic candidate for systemic aging intervention. This study shows that nasal mucosa-derived extracellular vesicles (nmEVs) exert systemic anti-ageing effects in mice by restoring circadian rhythm, suppressing cellular senescence, and improving cognitive function. In aged human bone marrow mesenchymal stem cells, nmEVs reverse senescence-associated phenotypes and reactivate core clock gene expression. Abstract Aging impairs tissue function and regenerative capacity across multiple organs. This study demonstrates that extracellular vesicles derived from human nasal mucosa (nmEVs) exert systemic antiaging effects in aged mice. Treatment with nmEVs improves cognitive performance and alters hippocampal aging signatures related to synaptic signaling and the regulation of neuroplasticity. In parallel, transcriptomic analysis of five major aging-sensitive organs reveals that nmEVs broadly ameliorate age-associated transcriptional changes, notably by restoring circadian rhythmicity and suppressing cellular senescence-related pathways. At the cellular level, nmEVs alleviate senescence phenotypes in aged human bone marrow mesenchymal stem cells, restore proliferation and osteogenic capacity, and reactivate core clock gene expression. These effects are accompanied by modulation of the p53 pathway, suggesting its involvement in nmEV-mediated rejuvenation. Importantly, lacking the need for cell isolation and ex vivo expansion, nmEVs offer a practical, age-independent source of extracellular vesicles with high clinical accessibility. Together, these findings support the translational potential of nmEVs as a multifaceted therapeutic candidate for systemic aging intervention. Advanced Science, EarlyView.