DDS promotes longevity through a microbiome-mediated starvation signal

Haeri Choi; Sung Chun Cho; Young Wan Ha; Billie Ocampo; Shirley Park; Shiwen Chen; Christopher F. Bennett; Jeehae Han; Ryan Rossner; Jong-Sun Kang; Yun-ll Lee; Sang Chul Park; Matt Kaeberlein

Translational Medicine of Aging (Jan 2019)

DDS promotes longevity through a microbiome-mediated starvation signal

Haeri Choi,
Sung Chun Cho,
Young Wan Ha,
Billie Ocampo,
Shirley Park,
Shiwen Chen,
Christopher F. Bennett,
Jeehae Han,
Ryan Rossner,
Jong-Sun Kang,
Yun-ll Lee,
Sang Chul Park,
Matt Kaeberlein

Affiliations

Haeri Choi: Department of Obstetrics & Gynecology, Oregon Health and Science University, Portland, OR, 97239, USA; Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, 97239, USA
Sung Chun Cho: Well Aging Research Center, Daegu Geongbuk Institute Science and Technology (DGIST), Daegu, 42988, South Korea
Young Wan Ha: Well Aging Research Center, Samsung Advanced Institute of Technology (SAIT), Suwon, South Korea
Billie Ocampo: Department of Pathology, University of Washington, Seattle, WA, USA
Shirley Park: Department of Pathology, University of Washington, Seattle, WA, USA
Shiwen Chen: Department of Pathology, University of Washington, Seattle, WA, USA
Christopher F. Bennett: Department of Pathology, University of Washington, Seattle, WA, USA
Jeehae Han: Department of Pathology, University of Washington, Seattle, WA, USA
Ryan Rossner: Department of Pathology, University of Washington, Seattle, WA, USA
Jong-Sun Kang: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea; Samsung Biomedical Institute, Samsung Medical Center, Seoul, 06351, South Korea
Yun-ll Lee: Well Aging Research Center, Daegu Geongbuk Institute Science and Technology (DGIST), Daegu, 42988, South Korea
Sang Chul Park: Well Aging Research Center, Daegu Geongbuk Institute Science and Technology (DGIST), Daegu, 42988, South Korea; The Future Life and Society Research Center, Chonnam National University, Gwangju, South Korea
Matt Kaeberlein: Department of Pathology, University of Washington, Seattle, WA, USA; Corresponding author.

Journal volume & issue: Vol. 3
pp. 64 – 69

Abstract

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The antibiotic diaminodiphenyl sulfone (DDS) is used in combination with other antibiotics as a first line treatment for leprosy. DDS has been previously reported to extend lifespan in Caenorhabditis elegans through inhibition of pyruvate kinase and decreased mitochondrial function. Here we report an alternative mechanism of action by which DDS promotes longevity in C. elegans by reducing folate production by the microbiome. This results in altered methionine cycle metabolite levels mimicking the effects of metformin and lifespan extension that is dependent on the starvation- and hypoxia-induced flavin containing monoxygenase, FMO-2.

Published in Translational Medicine of Aging

ISSN: 2468-5011 (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Medicine
Website: https://www.keaipublishing.com/en/journals/translational-medicine-of-aging/

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