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Dietary Restriction Improves Intestinal Cellular Fitness to Enhance Gut Barrier Function and Lifespan in D. Melanogaster

48 Pages Posted: 4 Apr 2018 Sneak Peek Status: Review Complete

See all articles by Kazutaka Akagi

Kazutaka Akagi

National Center for Geriatrics and Gerontology

Kenneth A. Wilson

Buck Institute for Research on Aging

Subhash D. Katewa

Buck Institute for Research on Aging

Mauricio Ortega

Buck Institute for Research on Aging

Jesse Simmons

Buck Institute for Research on Aging

Subir Kapuria

Buck Institute for Research on Aging

Amit Sharma

Buck Institute for Research on Aging

Heinrich Jasper

affiliation not provided to SSRN

Pankaj Kapahi

Buck Institute for Research on Aging

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Abstract

Loss of gut integrity is linked to various human diseases including inflammatory bowel disease. However, the mechanisms which lead to loss of barrier function remain poorly understood. Using D. melanogaster, we demonstrate that dietary restriction (DR) slows the age-related decline in intestinal integrity by enhancing enterocyte cellular fitness through upregulation of dMyc in the intestinal epithelium. Reduction of dMyc in enterocytes induces cell death through JNK signaling leading to increased gut permeability and reduced lifespan upon DR. Genetic mosaic and epistasis analyses suggest that cell competition, whereby neighboring cells eliminate unfit cells by apoptosis, mediates cell death in enterocytes with reduced levels of dMyc. Reducing enterocyte apoptosis partially rescued the increased gut permeability and shortened lifespan upon loss of dMyc. We propose that dMyc acts as a barometer of enterocyte cell fitness impacting intestinal homeostasis in response to changes in diet and age.

Suggested Citation

Akagi, Kazutaka and Wilson, Kenneth A. and Katewa, Subhash D. and Ortega, Mauricio and Simmons, Jesse and Kapuria, Subir and Sharma, Amit and Jasper, Heinrich and Kapahi, Pankaj, Dietary Restriction Improves Intestinal Cellular Fitness to Enhance Gut Barrier Function and Lifespan in D. Melanogaster (2018). Available at SSRN: https://ssrn.com/abstract=3155743 or http://dx.doi.org/10.2139/ssrn.3155743
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Kazutaka Akagi (Contact Author)

National Center for Geriatrics and Gerontology ( email )

7-430 Morioka-cho
Obu, Aichi
Japan

Kenneth A. Wilson

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Subhash D. Katewa

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Mauricio Ortega

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Jesse Simmons

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Subir Kapuria

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Amit Sharma

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Heinrich Jasper

affiliation not provided to SSRN

Pankaj Kapahi

Buck Institute for Research on Aging ( email )

8001 Redwood Boulevard
Novato, CA 94945
United States

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