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Microbial Genetic Composition Tunes Host Longevity
- Source :
- Cell. 173(4)
- Publication Year :
- 2018
-
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 (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-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.
- Subjects :
- 0301 basic medicine
Aging
media_common.quotation_subject
Mutant
Longevity
medicine.disease_cause
Mitochondrial Dynamics
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Polysaccharides
Mitochondrial unfolded protein response
medicine
Escherichia coli
Animals
Secretion
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Transcription factor
media_common
Genetics
Amyloid beta-Peptides
biology
biology.organism_classification
Bacterial Load
030104 developmental biology
Models, Animal
Unfolded protein response
Unfolded Protein Response
Gene Deletion
Genome-Wide Association Study
Transcription Factors
Subjects
Details
- ISSN :
- 10974172
- Volume :
- 173
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....9f4dd9a5f04737e3b19db0ad4d86bb7d