Photinia glabra-derived exosome-like nanovesicles mitigate skin inflammaging via dual regulation of inflammatory signaling and calcium homeostasis

Chronic low-grade inflammation accelerates skin aging, termed inflammaging. This study investigates whether Photinia glabra-derived exosome-like nanovesicles (PgELNs) can alleviate inflammaging by modulating inflammatory signaling and calcium homeostasis. PgELNs were isolated using tangential flow filtration and characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Human keratinocytes (HaCaT) were stimulated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) to model inflammaging. PgELN uptake, cell viability, senescence markers, cytokine expression, tight junction proteins, and calcium levels were assessed via flow cytometry, quantitative Real-Time Polymerase Chain Reaction (RT-PCR), immunoblotting, and transcriptomic profiling. PgELNs were efficiently internalized without cytotoxicity. In stimulated cells, PgELNs reduced proinflammatory cytokines, senescence-associated secretory phenotype (SASP) markers, and restored IL-10 and tight junction proteins. Transcriptome and pathway analyses revealed suppression of JAK/STAT signaling via STAT1 and ISG15 downregulation, reducing CXCL9/10 expression. This led to normalization of intracellular and extracellular Ca2+ levels. PgELNs mitigate skin inflammaging by dual regulation of inflammation and calcium homeostasis. Targeting the STAT1–CXCL9/10 axis, PgELNs reduce senescence and preserve barrier integrity. These findings highlight PgELNs as a promising plant-derived nanotherapeutic for managing inflammation-associated skin aging.