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Longevity in Mice Is Promoted by Probiotic-Induced Suppression of Colonic Senescence Dependent on Upregulation of Gut Bacterial Polyamine Production
Open accessAbstract
BACKGROUND: Chronic low-grade inflammation is recognized as an important factor contributing to senescence and age-related diseases. In mammals, levels of polyamines (PAs) decrease during the ageing process; PAs are known to decrease systemic inflammation by inhibiting inflammatory cytokine synthesis in macrophages. Reductions in intestinal luminal PAs levels have been associated with intestinal barrier dysfunction. The probiotic strain Bifidobacterium animalis subsp. lactis LKM512 is known to increase intestinal luminal PA concentrations. METHODOLOGY/PRINCIPAL FINDINGS: We supplemented the diet of 10-month-old Crj:CD-1 female mice with LKM512 for 11 months, while the controls received no supplementation. Survival rates were compared using Kaplan-Meier survival curves. LKM512-treated mice survived significantly longer than controls (P<0.001); moreover, skin ulcers and tumors were more common in the control mice. We then analyzed inflammatory and intestinal conditions by measuring several markers using HPLC, ELISA, reverse transcription-quantitative PCR, and histological slices. LKM512 mice showed altered 16S rRNA gene expression of several predominant intestinal bacterial groups. The fecal concentrations of PAs, but not of short-chain fatty acids, were significantly higher in LKM512-treated mice (P<0.05). Colonic mucosal function was also better in LKM512 mice, with increased mucus secretion and better maintenance of tight junctions. Changes in gene expression levels were evaluated using the NimbleGen mouse DNA microarray. LKM512 administration also downregulated the expression of ageing-associated and inflammation-associated genes and gene expression levels in 21-month-old LKM512-treated mice resembled those in 10-month-old untreated (younger) mice. CONCLUSION/SIGNIFICANCE: Our study demonstrated increased longevity in mice following probiotic treatment with LKM512, possibly due to the suppression of chronic low-grade inflammation in the colon induced by higher PA levels. This indicates that ingestion of specific probiotics may be an easy approach for improving intestinal health and increasing lifespan. Further studies are required to clarify its effectiveness in humans.
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“Similarly, nutrient supplementation with polyamine preparations containing spermidine or provision of a polyamine-producing gut flora increases longevity in mice (Matsumoto et al., 2011; Soda et al., 2009).”
From The Hallmarks of Aging (2013) · cites this paper as Matsumoto et al., 2011
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“Members of the Bifidobacteriaceae, Akkermansiaceae, and Eubacteriaceae families that are associated with beneficial effects on intestinal and extra-intestinal health in both mice and humans”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [78]
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“B. animalis, a probiotic species positively associated with longevity in mice [78] and negatively correlated with inflammation and human obesity [81]”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [78]
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“Polyamines exhibit numerous beneficial effects including increased longevity, recovery of injured mucosa, as well as favorable effects on cognitive function.122, 123, 124”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [124]
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López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
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Regulation of Intestinal Barrier Function by Microbial Metabolites
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Metadata
- Authors
- Matsumoto, M., Kurihara, S., Kibe, R., Ashida, H., & Benno, Y.
- Affiliations
- RIKEN (JP)
- Kyoto University (JP)
- Corresponding author
- Matsumoto, Mitsuharu
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-08-16
- Volume
- 6
- Issue
- 8
- Pages
- e23652
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3156754
- OpenAlex
- W2164188362
- Cited by
- 290
- References
- 60
- Citations by year
- 2026: 10 · 2025: 30 · 2024: 19 · 2023: 27 · 2022: 29 · 2021: 38 · 2020: 15 · 2019: 25 · 2018: 23 · 2017: 16 · 2016: 10 · 2015: 8 · 2014: 18 · 2013: 14 · 2012: 8
- FWCI
- 18.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- probiotics, polyamines, longevity, lifespan extension, low-grade inflammation, gut microbiota, intestinal barrier function, mucus secretion, tight junctions, skin ulcers
- MeSH terms
- Animals, Bacteria, Bifidobacterium, Colon, Feces, Female, Longevity, Mice, Inbred ICR, Mucus, Neoplasms, Polyamines, RNA, Ribosomal, 16S, Skin Ulcer, Spermine, Gene Expression Regulation, Bacterial, Cellular Senescence, Tight Junctions, Probiotics, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice, Kaplan-Meier Estimate
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