Mechanisms driving fasting-induced protection from genotoxic injury in the small intestine

Author:

Deans-Fielder Kali123ORCID,Wu Timothy34,Nguyen Thanh15,To Sarah1,Huang Yang-Zhe15,Bark Steven J.1,Mills Jason C.167ORCID,Shroyer Noah F.124ORCID

Affiliation:

1. Division of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States

2. Translational Biology and Molecular Medicine Graduate Program, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, Texas, United States

3. Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas, United States

4. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

5. Cancer and Cell Biology Graduate Program, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, Texas, United States

6. Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States

7. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States

Abstract

New findings are 1) DNA damage reduction following a 24-h fast depends on the timing of postfast refeeding in relation to chemotherapy initiation; 2) fasting/refeeding-induced upregulation of mTORC1 activity is not required for early (6 h) protection against DXR-induced DNA damage; and 3) fasting increases expression of intestinal stem cell and DNA damage repair genes, even when mTORC1 is dysregulated, highlighting fasting’s crucial role in regulating mTORC1-dependent and independent mechanisms in the dynamic recovery process.

Funder

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

American Physiological Society

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