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Cell-Free Culture Supernatant of Probiotic Lactobacillus fermentum Protects Against H2O2-Induced Premature Senescence by Suppressing ROS-Akt-mTOR Axis in Murine Preadipocytes

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Abstract

Information regarding cellular anti-senescence attributes of probiotic bacteria vis-à-vis modulation of senescence-associated secretory phenotype (SASP) and mTOR signaling is very limited. The present study assessed anti-senescence potential of secretory metabolites of probiotic Lactobacillus fermentum (Lact. fermentum) using H2O2-induced model of senescence in 3T3-L1 preadipocytes. Application of H2O2-induced cellular senescence characterized by increased cell size and SA-β-gal activity, activation of SASP and reactive oxygen species (ROS), DNA damage response and induction of cell cycle inhibitors (p53/p21WAF1/p16INK4a). Further, a robust stimulation of the PI3K/Akt/mTOR pathway and AMPK signaling was also observed in H2O2-treated cells. However, exposure of cells to cell-free supernatant of Lact. fermentum significantly attenuated phosphorylation of PI3K/Akt/mTOR pathway and alleviated senescence markers p53, p21WAF1, SA-β-gal, p38MAPK, iNOS, cox-2, ROS, NF-κB, and DNA damage response. These results provide evidence that secretory metabolites of Lact. fermentum can mitigate the development as well as severity of stress-induced senescence thereby indicating its utility for use as anti-aging or age-delaying agent.

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Funding

This work was supported by grants from Department of Science and Technology, Government of India, under the INSPIRE Faculty scheme (IFA17-LSPA79). The CSIR-IHBT publication number of this manuscript is 4350.

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  1. Pharmacology and Toxicology Laboratory, Food & Nutraceutical Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, India

    Ravi Kumar, Anamika Sharma, Yogendra Padwad & Rohit Sharma

  2. Food & Nutraceutical Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, India

    Mahesh Gupta

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  1. Ravi Kumar
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Kumar, R., Sharma, A., Gupta, M. et al. Cell-Free Culture Supernatant of Probiotic Lactobacillus fermentum Protects Against H2O2-Induced Premature Senescence by Suppressing ROS-Akt-mTOR Axis in Murine Preadipocytes. Probiotics & Antimicro. Prot. 12, 563–576 (2020). https://doi.org/10.1007/s12602-019-09576-z

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