Abstract
Aging is characterized by progressive loss of skin elasticity, reduced motor performance, cognitive decline, and deterioration of multiple organ systems. Developing effective anti-aging interventions is crucial for mitigating these degenerative changes. This study aimed to investigate the protective effects of Lactobacillus-derived extracellular vesicles derived from Limosilactobacillus fermentum strain F-B9-1-2 (LDEVs) D-galactose (D-gal)-induced mice, using nicotinamide mononucleotide (NMN) as a positive control. LDEVs were isolated and characterized by electron microscopy and nanoparticle tracking analysis. In vitro, LDEVs significantly enhanced the viability of human umbilical vein endothelial cells (HUVECs) and markedly attenuated D-galactose–induced cellular senescence, as evidenced by reduced senescence-associated β-galactosidase staining. In vivo, behavioral assessments showed that LDEVs administration improved spontaneous locomotor activity and learning–memory performance in D-gal–induced mice. Biochemical analyses showed that LDEVs modulated tissue-specific functional and aging-related markers in the skin, brain, and liver. RT-qPCR analysis indicated downregulation of p16, p19, and p21 expression in the liver and brain, as well as IL-6 expression in the skin. Histological examinations of hippocampal and cutaneous tissues further supported the protective role of LDEVs. Collectively, these findings indicate that LDEVs are associated with attenuation of D-gal–induced aging-like phenotypes in mice, accompanied by reduced cellular senescence, inflammation, and oxidative stress. This study provides preliminary evidence supporting the potential of probiotic-derived extracellular vesicles as candidate anti-aging agents, warranting further validation in naturally aged models and mechanistic investigations.
Data availability
The 16 S rRNA gene sequence of Limosilactobacillus fermentum F-B9-1-2 generated in this study has been deposited in the NCBI GenBank database under accession number PZ053904. Other data supporting the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
This work was supported by Key Innovation Project of Qilu University of Technology (Shandong Academy of Sciences) (2025ZDZX14), National Key R&D Program Intergovernmental International Science and Technology Innovation Cooperation Project (2023YFE0111900).
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This work was supported by Key Innovation Project of Qilu University of Technology (Shandong Academy of Sciences) (2025ZDZX14), National Key R&D Program Intergovernmental International Science and Technology Innovation Cooperation Project (2023YFE0111900).
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Writing—original draft preparation, Z.W., S.Z. and X.L.; methodology, Z.W. and S.Z.; software, Z.W. and K.Z.; validation, Q.Y. and L.T.; formal analysis, X.L.; investigation, X.S.; resources, L.S. and L.Z.; data curation, Z.W.; writing—review and editing, Z.W., S.Z. and L.S.; visualization, Z.W.; supervision, L.S. and L.Z.; funding acquisition, L.S. and L.Z. All authors have read and agreed to the published version of the manuscript.
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Wang, Z., Zhang, S., Li, X. et al. Anti-aging potential of Limosilactobacillus fermentum F-B9-1-2 extracellular vesicles in D-galactose–induced cellular and organ senescence . Sci Rep (2026). https://doi.org/10.1038/s41598-026-43553-1
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DOI: https://doi.org/10.1038/s41598-026-43553-1
