Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):E7506-E7515. doi: 10.1073/pnas.1706464114. Epub 2017 Aug 21.

Indoles from commensal bacteria extend healthspan.

Author information

1
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
2
Emory Vaccine Center, Emory University, Atlanta, GA 30329.
3
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
4
Yerkes National Primate Research Center, Lawrenceville, GA 30043.
5
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.
6
Department of Biology, McMaster University, Hamilton, ON, Canada L8S 4K1.
7
Immunology and Molecular Pathogenesis Graduate Program, Emory University School of Medicine, Atlanta, GA 30322.
8
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.
9
Division of Geriatric Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322.
10
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; dkalman@emory.edu.

Abstract

Multiple studies have identified conserved genetic pathways and small molecules associated with extension of lifespan in diverse organisms. However, extending lifespan does not result in concomitant extension in healthspan, defined as the proportion of time that an animal remains healthy and free of age-related infirmities. Rather, mutations that extend lifespan often reduce healthspan and increase frailty. The question arises as to whether factors or mechanisms exist that uncouple these processes and extend healthspan and reduce frailty independent of lifespan. We show that indoles from commensal microbiota extend healthspan of diverse organisms, including Caenorhabditis elegans, Drosophila melanogaster, and mice, but have a negligible effect on maximal lifespan. Effects of indoles on healthspan in worms and flies depend upon the aryl hydrocarbon receptor (AHR), a conserved detector of xenobiotic small molecules. In C. elegans, indole induces a gene expression profile in aged animals reminiscent of that seen in the young, but which is distinct from that associated with normal aging. Moreover, in older animals, indole induces genes associated with oogenesis and, accordingly, extends fecundity and reproductive span. Together, these data suggest that small molecules related to indole and derived from commensal microbiota act in diverse phyla via conserved molecular pathways to promote healthy aging. These data raise the possibility of developing therapeutics based on microbiota-derived indole or its derivatives to extend healthspan and reduce frailty in humans.

KEYWORDS:

C. elegans; aging; aryl hydrocarbon receptor; frailty; microbiota

PMID:
28827345
PMCID:
PMC5594673
DOI:
10.1073/pnas.1706464114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center