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<p>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 <i>Lactobacillus</i>-derived extracellular vesicles derived from <i>Limosilactobacillus fermentum</i> 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.</p>

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Anti-aging potential of Limosilactobacillus fermentum F-B9-1-2 extracellular vesicles in D-galactose–induced cellular and organ senescence 

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月2日

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  • Zhihao Wang,
  • Song Zhang,
  • Xiaowei Li,
  • Xin Sun,
  • Qiulin Yue,
  • Kai Zheng,
  • Li Tian,
  • Le Su,
  • Lin Zhao

摘要

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.