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Microbial Genetic Composition Tunes Host Longevity.
- Source :
-
Cell [Cell] 2017 Jun 15; Vol. 169 (7), pp. 1249-1262.e13. - Publication Year :
- 2017
-
Abstract
- Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPR <superscript>mt</superscript> ) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPR <superscript>mt</superscript> -responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Aging metabolism
Amyloid beta-Peptides metabolism
Animals
Bacterial Load
Caenorhabditis elegans metabolism
Caenorhabditis elegans Proteins metabolism
Escherichia coli metabolism
Gene Deletion
Genome-Wide Association Study
Mitochondrial Dynamics
Models, Animal
Polysaccharides metabolism
Transcription Factors metabolism
Unfolded Protein Response
Caenorhabditis elegans microbiology
Escherichia coli genetics
Longevity
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 169
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 28622510
- Full Text :
- https://doi.org/10.1016/j.cell.2017.05.036