Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

Indoles from commensal bacteria extend healthspan

Robert Sonowal, Alyson Swimm, Anusmita Sahoo, Liping Luo, Yohei Matsunaga, Ziqi Wu, Jui A. Bhingarde, Elizabeth A. Ejzak, Ayush Ranawade, Hiroshi Qadota, Domonica N. Powell, Christopher T. Capaldo, Jonathan M. Flacker, Rhienallt M. Jones, Guy M. Benian, and Daniel Kalman
PNAS September 5, 2017 114 (36) E7506-E7515; first published August 21, 2017; https://doi.org/10.1073/pnas.1706464114
Robert Sonowal
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alyson Swimm
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anusmita Sahoo
bEmory Vaccine Center, Emory University, Atlanta, GA 30329;
cDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;
dYerkes National Primate Research Center, Lawrenceville, GA 30043;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Liping Luo
eDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yohei Matsunaga
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ziqi Wu
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jui A. Bhingarde
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth A. Ejzak
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ayush Ranawade
fDepartment of Biology, McMaster University, Hamilton, ON, Canada L8S 4K1;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Qadota
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Domonica N. Powell
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
gImmunology and Molecular Pathogenesis Graduate Program, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher T. Capaldo
hDepartment of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonathan M. Flacker
iDivision of Geriatric Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rhienallt M. Jones
eDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Guy M. Benian
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel Kalman
aDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dkalman@emory.edu
  1. Edited by Frederick M. Ausubel, Harvard Medical School and Massachusetts General Hospital, Boston, MA, and approved July 21, 2017 (received for review April 19, 2017)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

Increases in human life expectancy over the next century will be accompanied by increased frailty and massive and unsustainable health care costs. Developing means to extend the time that individuals remain healthy and free of age-related infirmities, called healthspan, has therefore become a critical goal of aging research. We show that small molecules produced by the microbiota and related to indole extend healthspan in geriatric worms, flies, and mice, without attendant effects on lifespan. Indoles act via the aryl hydrocarbon receptor and cause animals to retain a youthful gene expression profile. Indoles may represent a new class of therapeutics that improve the way we age as opposed to simply extending how long we live.

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.

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

Footnotes

  • ↵1To whom correspondence should be addressed. Email: dkalman{at}emory.edu.
  • Author contributions: R.S., A. Swimm, Y.M., H.Q., J.M.F., R.M.J., G.M.B., and D.K. designed research; R.S., A. Swimm, L.L., Y.M., Z.W., J.A.B., E.A.E., H.Q., D.N.P., and C.T.C. performed research; R.S. contributed new reagents/analytic tools; R.S., A. Swimm, A. Sahoo, L.L., A.R., H.Q., D.N.P., C.T.C., and D.K. analyzed data; and R.S. and D.K. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The raw RNA-Seq data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, https://www.ncbi.nlm.nih.gov/geo (accession no. GSE101910).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1706464114/-/DCSupplemental.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Indoles from commensal bacteria extend healthspan
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Indoles and healthspan
Robert Sonowal, Alyson Swimm, Anusmita Sahoo, Liping Luo, Yohei Matsunaga, Ziqi Wu, Jui A. Bhingarde, Elizabeth A. Ejzak, Ayush Ranawade, Hiroshi Qadota, Domonica N. Powell, Christopher T. Capaldo, Jonathan M. Flacker, Rhienallt M. Jones, Guy M. Benian, Daniel Kalman
Proceedings of the National Academy of Sciences Sep 2017, 114 (36) E7506-E7515; DOI: 10.1073/pnas.1706464114

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Indoles and healthspan
Robert Sonowal, Alyson Swimm, Anusmita Sahoo, Liping Luo, Yohei Matsunaga, Ziqi Wu, Jui A. Bhingarde, Elizabeth A. Ejzak, Ayush Ranawade, Hiroshi Qadota, Domonica N. Powell, Christopher T. Capaldo, Jonathan M. Flacker, Rhienallt M. Jones, Guy M. Benian, Daniel Kalman
Proceedings of the National Academy of Sciences Sep 2017, 114 (36) E7506-E7515; DOI: 10.1073/pnas.1706464114
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 114 (36)
Table of Contents

Submit

Sign up for Article Alerts

Article Classifications

  • Biological Sciences
  • Genetics

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Surgeons hands during surgery
Inner Workings: Advances in infectious disease treatment promise to expand the pool of donor organs
Despite myriad challenges, clinicians see room for progress.
Image credit: Shutterstock/David Tadevosian.
Setting sun over a sun-baked dirt landscape
Core Concept: Popular integrated assessment climate policy models have key caveats
Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Double helix
Journal Club: Noncoding DNA shown to underlie function, cause limb malformations
Using CRISPR, researchers showed that a region some used to label “junk DNA” has a major role in a rare genetic disorder.
Image credit: Nathan Devery.
Steamboat Geyser eruption.
Eruption of Steamboat Geyser
Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018.
Listen
Past PodcastsSubscribe
Birds nestling on tree branches
Parent–offspring conflict in songbird fledging
Some songbird parents might improve their own fitness by manipulating their offspring into leaving the nest early, at the cost of fledgling survival, a study finds.
Image credit: Gil Eckrich (photographer).

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490