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Rapamycin modulates tissue aging and lifespan independently of the gut microbiota in Drosophila

Schinaman, Joseph M.; Rana, Anil; Ja, William W.; Clark, Rebecca I.; Walker, David W.

Rapamycin modulates tissue aging and lifespan independently of the gut microbiota in Drosophila Thumbnail


Authors

Joseph M. Schinaman

Anil Rana

William W. Ja

David W. Walker



Abstract

The FDA approved drug rapamycin can prolong lifespan in diverse species and delay the onset of age-related disease in mammals. However, a number of fundamental questions remain unanswered regarding the mechanisms by which rapamycin modulates age-related pathophysiology and lifespan. Alterations in the gut microbiota can impact host physiology, metabolism and lifespan. While recent studies have shown that rapamycin treatment alters the gut microbiota in aged animals, the causal relationships between rapamycin treatment, microbiota dynamics and aging are not known. Here, using Drosophila as a model organism, we show that rapamycin-mediated alterations in microbiota dynamics in aged flies are associated with improved markers of intestinal and muscle aging. Critically, however, we show that the beneficial effects of rapamycin treatment on tissue aging and lifespan are not dependent upon the microbiota. Indeed, germ-free flies show delayed onset of intestinal barrier dysfunction, improved proteostasis in aged muscles and a significant lifespan extension upon rapamycin treatment. In contrast, genetic inhibition of autophagy impairs the ability of rapamycin to mediate improved gut health and proteostasis during aging. Our results indicate that rapamycin-mediated modulation of the microbiota in aged animals is not causally required to slow tissue and organismal aging.

Citation

Schinaman, J. M., Rana, A., Ja, W. W., Clark, R. I., & Walker, D. W. (2019). Rapamycin modulates tissue aging and lifespan independently of the gut microbiota in Drosophila. Scientific Reports, 9(1), Article 7824. https://doi.org/10.1038/s41598-019-44106-5

Journal Article Type Article
Acceptance Date May 9, 2019
Online Publication Date May 24, 2019
Publication Date May 24, 2019
Deposit Date Jun 11, 2019
Publicly Available Date Mar 28, 2024
Journal Scientific Reports
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 9
Issue 1
Article Number 7824
DOI https://doi.org/10.1038/s41598-019-44106-5

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http://creativecommons.org/licenses/by/4.0/

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This article is licensed under a
Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.




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