Indoles from commensal bacteria extend healthspan

• Type of Material: Article
• Authors: Robert Sonowal, Emory University; Alyson Swimm, Emory University; Anusmita Sahoo, Emory University; Liping Luo, Emory University; Yohei Matsunaga, Emory University; Ziqi Wu, Emory University; Jui A. Bhingarde, Emory University; Elizabeth A. Ejzak, Emory University; Aysh Ranawade, McMaster University; Hiroshi Qadota, Emory University; Daniel Powell, Emory University; Christopher T. Capaldo, Emory University; Jonathan Flacker, Emory University; Rheinallt M Jones, Emory University; Guy Benian, Emory University; Daniel Kalman, Emory University
• Language: English
• Date: 2017-09-05
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2017, National Academy of Sciences. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1706464114
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• ISSN: 0027-8424
• Volume: 114
• Issue: 36
• Start Page: E7506
• End Page: E7515
• Grant/Funding Information: This work was supported by grants from Bio-Merieux Foundation and NIH (2R01DK074731-04A1) (to D.K.). The Bloomington Drosophila Stock Centre, which provided Drosophila lines, is supported by NIH Grant P40OD018537.
• Keywords: ESCHERICHIA-COLI; CELL; microbiota; aging; INTESTINE; DISEASE; Science & Technology; ARYL-HYDROCARBON RECEPTOR; frailty; TRANSPLANTATION; LIFE-SPAN; Multidisciplinary Sciences; C. elegans; C. ELEGANS; aryl hydrocarbon receptor; CAENORHABDITIS-ELEGANS; Science & Technology - Other Topics; GUT MICROBIOTA
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery; Biology, Cell

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.