| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Kumar, Arun Saha, Manti Kumar Kumar, Vipin Bhattacharya, Anupam Barge, Sagar Mukherjee, Ashis K. Kalita, Mohan C. Khan, Mojibur R. |
| Abstract | Background Proteostasis is a critical aging hallmark responsible for removing damaged or misfolded proteins and their aggregates by improving proteasomal degradation through the autophagy-lysosome pathway (ALP) and the ubiquitin–proteasome system (UPS). Research on the impact of heat-killed probiotic bacteria and their structural components on aging hallmarks and innate immune responses is scarce, yet enhancing these effects could potentially delay age-related diseases. Results This study introduces a novel heat-killed Levilactobacillus brevis strain MKAK9 (HK MKAK9), along with its exopolysaccharide (EPS), demonstrating their ability to extend longevity by improving proteostasis and immune responses in wild-type Caenorhabditis elegans. We elucidate the underlying mechanisms through a comprehensive approach involving mRNA- and small RNA sequencing, proteomic analysis, lifespan assays on loss-of-function mutants, and quantitative RT-PCR. Mechanistically, HK MKAK9 and its EPS resulted in downregulation of the insulin-like signaling pathway in a DAF-16-dependent manner, enhancing protein ubiquitination and subsequent proteasomal degradation through activation of the ALP pathway, which is partially mediated by microRNA mir-243. Importantly, autophagosomes engulf ubiquitinylated proteins, as evidenced by increased expression of the autophagy receptor sqst-3, and subsequently fuse with lysosomes, facilitated by increased levels of the lysosome-associated membrane protein (LAMP) lmp-1, suggesting the formation of autolysosomes for degradation of the selected cargo. Moreover, HK MKAK9 and its EPS activated the p38 MAPK pathway and its downstream SKN-1 transcription factor, which are known to regulate genes involved in innate immune response (thn-1, ilys-1, cnc-2, spp-9, spp-21, clec-47, and clec-266) and antioxidation (sod-3 and gst-44), thereby reducing the accumulation of reactive oxygen species (ROS) at both cellular and mitochondrial levels. Notably, SOD-3 emerged as a transcriptional target of both DAF-16 and SKN-1 transcription factors. Conclusion Our research sets a benchmark for future investigations by demonstrating that heat-killed probiotic and its specific cellular component, EPS, can downregulate the insulin-signaling pathway, potentially improving the autophagy-lysosome pathway (ALP) for degrading ubiquitinylated proteins and promoting organismal longevity. Additionally, we discovered that increased expression of microRNA mir-243 regulates insulin-like signaling and its downstream ALP pathway. Our findings also indicate that postbiotic treatment may bolster antioxidative and innate immune responses, offering a promising avenue for interventions in aging-related diseases. |
| Related Links | https://immunityageing.biomedcentral.com/counter/pdf/10.1186/s12979-024-00457-w.pdf |
| Ending Page | 26 |
| Page Count | 26 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17424933 |
| DOI | 10.1186/s12979-024-00457-w |
| Journal | Immunity & Ageing |
| Issue Number | 1 |
| Volume Number | 21 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-08-02 |
| Access Restriction | Open |
| Subject Keyword | Immunology Geriatrics Gerontology Aging Public Health Clinical Nutrition Antibodies Lactobacillus Probiotics Longevity p38 MAPK signalling Autophagy-lysosome pathway miRNA HK MKAK9 Geriatrics/Gerontology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Aging Immunology |
| Journal Impact Factor | 5.2/2023 |
| 5-Year Journal Impact Factor | 6.4/2023 |
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