Elevated DNA damage without signs of aging in the short-sleeping Mexican cavefish
Open accessPublished version of a preprint
Abstract
Dysregulated sleep has widespread health consequences, including the accumulation of DNA damage. The Mexican tetra, Astyanax mexicanus , provides a powerful model to study the evolution and consequences of sleep loss. Multiple cave-adapted populations of this species have independently evolved reduced sleep compared to surface populations, yet show no obvious decline in healthspan or longevity. To examine whether evolved sleep loss is associated with DNA damage, we compared DNA damage response (DDR) and oxidative stress across populations. Cavefish exhibited elevated γH2AX in the brain and increased gut oxidative stress, consistent with chronic sleep deprivation. Following acute UV exposure, surface fish, but not cavefish, increased sleep and activated the photoreactivation repair pathway. Fibroblast cell lines derived from both populations confirmed diminished DDR and repair in cavefish, supporting an attenuated acute DNA damage response. Transcriptomic analysis revealed that many genes differentially expressed with aging in surface fish remain unchanged in cavefish, suggesting altered regulation of aging-related pathways. Together, these findings indicate that cavefish experience elevated cellular hallmarks of sleep deprivation yet exhibit resilience to its long-term consequences, highlighting an evolutionary model to investigate the mechanisms underlying sleep, DNA repair, and healthy aging.
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Cites
The central role of DNA damage in the ageing process
Schumacher, B., Pothof, J., Vijg, J., & Hoeijmakers, J. H. J. (2021) · Nature · doi:10.1038/s41586-021-03307-7 · Cited by 907 · see citing works
Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut
Vaccaro, A., Kaplan Dor, Y., Nambara, K., Pollina, E. A., Lin, C., Greenberg, M. E., & Rogulja, D. (2020) · Cell · doi:10.1016/j.cell.2020.04.049 · Cited by 541 · see citing works
SIRT6 is responsible for more efficient DNA double-strand break repair in long-lived species
Tian, X., Firsanov, D., Zhang, Z., Cheng, Y., Luo, L., Tombline, G., Tan, R., Simon, M., Henderson, S., Steffan, J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.043 · Cited by 353 · see citing works
Unearthing the phylogenetic roots of sleep
Allada, R., & Siegel, J. M. (2008) · Current Biology · doi:10.1016/j.cub.2008.06.033 · Cited by 280 · see citing works
Arble, D. M., Bass, J., Behn, C. D., Butler, M. P., Challet, E., Czeisler, C., Depner, C. M., Elmquist, J., Franken, P., Grandner, M. A., et al. (2015) · Sleep · doi:10.5665/sleep.5226 · Cited by 173 · cited 1× · see citing works
“For example, in humans, insomnia is associated with many different diseases and increased morbidity, suggesting that sleep is critical for healthy aging (Arble et al., 2015; Carroll and Prather, 2021).”
Self-citationCarroll, J. E., Cole, S. W., Seeman, T. E., Breen, E. C., Witarama, T., Arevalo, J. M. G., Ma, J., & Irwin, M. R. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.08.024 · Cited by 129 · see citing works
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- Authors
- Lloyd, E., Xia, F., Moore, K., Zertuche Mery, C., Rastogi, A., Kozol, R. A., Kenzor, O., Warren, W., Appelbaum, L., Moran, R. L., Zhao, C., Duboue, E. R., Rohner, N., & Keene, A. C.
- Affiliations
- Texas A&M University (US)
- Stowers Institute for Medical Research (US)
- Department of Biology, Texas A&M University
- Florida Atlantic University (US)
- Stowers Institute for Medical Research
- University of Missouri (US)
- Bar-Ilan University (IL)
- Harriet Wilkes Honors College, Florida Atlantic University
- Corresponding author
- Keene, Alex C
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2025-11-14
- Volume
- 13
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC11042282
- OpenAlex
- W4394984282
- Cited by
- 5
- References
- 6
- Citations by year
- 2026: 2 · 2025: 3
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (R24OB030214, NS122166)
- Israel Science Foundation (2021177)
- Topics
- Physical Sciences › Earth and Planetary Sciences › Paleontology › Subterranean biodiversity and taxonomy
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- sleep deprivation, cavefish, Astyanax mexicanus, DNA damage response, DNA repair, oxidative stress, γH2AX, UV-induced DNA damage, aging, longevity, healthspan, embryonic fibroblasts, transcriptome, brain, intestine, sleep evolution, neurodegeneration
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