Cited by 542Genetics, Aging, and Longevity in Model OrganismsCircadian rhythm and melatoninSleep and Wakefulness Research

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Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut

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Vaccaro, Alexandra, Kaplan Dor, Yosef, Nambara, Keishi, Pollina, Elizabeth A., Lin, Cindy, Greenberg, Michael E., Rogulja, Dragana·2020·Cell

DOI 10.1016/j.cell.2020.04.049

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Abstract

The view that sleep is essential for survival is supported by the ubiquity of this behavior, the apparent existence of sleep-like states in the earliest animals, and the fact that severe sleep loss can be lethal. The cause of this lethality is unknown. Here we show, using flies and mice, that sleep deprivation leads to accumulation of reactive oxygen species (ROS) and consequent oxidative stress, specifically in the gut. ROS are not just correlates of sleep deprivation but drivers of death: their neutralization prevents oxidative stress and allows flies to have a normal lifespan with little to no sleep. The rescue can be achieved with oral antioxidant compounds or with gut-targeted transgenic expression of antioxidant enzymes. We conclude that death upon severe sleep restriction can be caused by oxidative stress, that the gut is central in this process, and that survival without sleep is possible when ROS accumulation is prevented. VIDEO ABSTRACT.

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Authors: Vaccaro, A., Kaplan Dor, Y., Nambara, K., Pollina, E. A., Lin, C., Greenberg, M. E., & Rogulja, D.
Affiliations: Harvard University (US)
Corresponding author: Rogulja, Dragana
ORCID: Vaccaro, Alexandra
Nambara, Keishi
Pollina, Elizabeth A.
Greenberg, Michael E.
Rogulja, Dragana
Venue: Cell
Publisher: Elsevier BV
Published: 2020-06
Volume: 181
Issue: 6
Pages: 1307-1328.e15
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2020.04.049
OpenAlex: W3033924751
Cited by: 541
References: 252
Citations by year: 2026: 79 · 2025: 127 · 2024: 109 · 2023: 92 · 2022: 63 · 2021: 53 · 2020: 18
FWCI: 18.77
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 375 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: Pew Charitable Trusts
New York Stem Cell Foundation
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords: sleep deprivation, reactive oxygen species, oxidative stress, intestine, antioxidant enzymes, lifespan, oral antioxidants, Drosophila, mice
MeSH terms: Animals, Antioxidants, Drosophila, Male, Mice, Inbred CBA, Mice, Inbred C57BL, Sleep, Sleep Deprivation, Reactive Oxygen Species, Oxidative Stress, Gastrointestinal Tract, Mice

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Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut

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