Elevated DNA Damage without Signs of Aging in the Short-Sleeping Mexican Cavefish

Authors & Affiliations

• Evan Lloyd, Fanning Xia, Kinsley Moore, Carolina Zertuche, Aakriti Rastogi, Rob Kozol, Olga Kenzior, Wesley Warren, Lior Appelbaum, Rachel L. Moran, Chongbei Zhao, Erik Duboue, Nicolas Rohner, Alex C. Keene
• Affiliations include Texas A&M University, Stowers Institute for Medical Research, Florida Atlantic University, University of Missouri, Bar Illan University.

Abstract Summary

• Sleep and Health: Dysregulation in sleep is linked to health issues including neurodegeneration.
• DNA Damage: Sleep loss is associated with DNA damage, suggesting sleep is crucial for DNA repair.
• Mexican Cavefish (Astyanax mexicanus): Short-sleeping cavefish do not show reduced healthspan/longevity despite DNA damage.
• Comparative Study: Differences in DNA damage response (DDR) and oxidative stress were observed between cave-adapted and surface fish.
• Findings: Cavefish showed elevated DNA damage but less DDR activation compared to surface fish.

Introduction

• Function of Sleep: Essential for neural connectivity, metabolism, immunity, learning, and memory.
• DNA Damage Role: Associated with sleep drive across species.
• Cavefish as a Model: Used to study genetic basis of sleep and evolutionary adaptations.

Results

DNA Damage and DDR in Cavefish

• Elevated DNA Damage: H2AX marker increased in cavefish brains, indicating more DNA damage compared to surface fish.
• Reactive Oxygen Species (ROS): Increased in cavefish guts, indicating cellular stress.
• UV Response: Surface fish sleep increased after UV exposure, unlike cavefish.

Transcriptional Analysis

• Gene Expression: UV treatment activated DNA repair genes in surface fish but not in cavefish.
• Cellular Assays: Cavefish cells showed diminished DNA repair capabilities.

Discussion

• Resilience to Sleep Loss: Cavefish evolved resilience mechanisms against sleep loss despite DNA damage.
• Evolutionary Implications: Cavefish adaptations provide insights into sleep regulation and DNA repair evolution.

Methods

Fish Husbandry

• Fish kept in controlled conditions; breeding stimulated by temperature changes and specific feeding.

Cellular and Molecular Methods

• Cell Lines: Derived from embryos, used to study UV-induced DNA damage.
• RNA Sequencing: Performed to analyze gene expression changes post UV exposure.

Conclusions

• Cavefish as a Model: Provide insights into the relationship between sleep, DNA damage, and longevity.
• Potential for Further Research: Mechanisms in cavefish can highlight resilience to biological stress and inform human health studies.