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Intestinal Snakeskin Limits Microbial Dysbiosis During Aging and Promotes Longevity

Salazar, Anna M.; Resnik-Docampo, Martin; Ulgherait, Matthew; Clark, Rebecca I.; Shirazu-Hiza, Mimi; Jones, D. Leanne; Walker, David W.

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Authors

Anna M. Salazar

Martin Resnik-Docampo

Matthew Ulgherait

Mimi Shirazu-Hiza

D. Leanne Jones

David W. Walker



Abstract

Intestinal barrier dysfunction is an evolutionarily conserved hallmark of aging, which has been linked to microbial dysbiosis, altered expression of occluding junction proteins, and impending mortality. However, the interplay between intestinal junction proteins, age-onset dysbiosis, and lifespan determination remains unclear. Here, we show that altered expression of Snakeskin (Ssk), a septate junction-specific protein, can modulate intestinal homeostasis, microbial dynamics, immune activity, and lifespan in Drosophila. Loss of Ssk leads to rapid and reversible intestinal barrier dysfunction, altered gut morphology, dysbiosis, and dramatically reduced lifespan. Remarkably, restoration of Ssk expression in flies showing intestinal barrier dysfunction rescues each of these phenotypes previously linked to aging. Intestinal up-regulation of Ssk protects against microbial translocation following oral infection with pathogenic bacteria. Furthermore, intestinal up-regulation of Ssk improves intestinal barrier function during aging, limits dysbiosis, and extends lifespan. Our findings indicate that intestinal occluding junctions may represent prolongevity targets in mammals.

Citation

Salazar, A. M., Resnik-Docampo, M., Ulgherait, M., Clark, R. I., Shirazu-Hiza, M., Jones, D. L., & Walker, D. W. (2018). Intestinal Snakeskin Limits Microbial Dysbiosis During Aging and Promotes Longevity. iScience, 9, 229-243. https://doi.org/10.1016/j.isci.2018.10.022

Journal Article Type Article
Acceptance Date Oct 19, 2018
Online Publication Date Oct 24, 2018
Publication Date Oct 24, 2018
Deposit Date Oct 30, 2018
Publicly Available Date Mar 29, 2024
Journal iScience
Publisher Cell Press
Peer Reviewed Peer Reviewed
Volume 9
Pages 229-243
DOI https://doi.org/10.1016/j.isci.2018.10.022

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