{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:58:04Z","timestamp":1776131884854,"version":"3.50.1"},"reference-count":52,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>In many animals, short-term fluctuations in environmental conditions in early life often exert long-term effects on adult physiology. In Drosophila, one ecologically relevant environmental variable is hypoxia. Drosophila larvae live on rotting, fermenting food rich in microorganisms \u2013 an environment characterized by low ambient oxygen. They have therefore evolved to tolerate hypoxia. While the acute effects of hypoxia in larvae have been well studied, whether early-life hypoxia affects adult physiology and fitness is less clear. Here we show that Drosophila exposed to hypoxia during their larval period subsequently show reduced starvation stress resistance and shorter lifespan as adults, with these effects being stronger in males. We find that these effects are associated with reduced whole-body insulin signaling but elevated TOR kinase activity, a manipulation known to reduce lifespan. We also identify a sexually dimorphic effect of larval hypoxia on adult nutrient storage and mobilization. Thus, we find that males, but not females, show elevated levels of lipids and glycogen. Moreover, we see that both males and females exposed to hypoxia as larvae show defective lipid mobilization upon starvation stress as adults. These data show how early-life hypoxia can exert persistent, sexually dimorphic, long-term effects on Drosophila adult physiology and lifespan.<\/jats:p>","DOI":"10.1242\/jeb.226027","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T15:10:10Z","timestamp":1601305810000},"source":"Crossref","is-referenced-by-count":13,"title":["Early-life hypoxia alters adult physiology and reduces stress resistance and lifespan in\n                    <i>Drosophila<\/i>"],"prefix":"10.1242","author":[{"given":"Danielle M.","family":"Polan","sequence":"first","affiliation":[{"name":"Clark H Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, Alberta Children's Hospital Research Institute, and Department of Biochemistry and Molecular Biology Calgary, University of Calgary, Alberta T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Alansari","sequence":"additional","affiliation":[{"name":"Clark H Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, Alberta Children's Hospital Research Institute, and Department of Biochemistry and Molecular Biology Calgary, University of Calgary, Alberta T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byoungchun","family":"Lee","sequence":"additional","affiliation":[{"name":"Clark H Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, Alberta Children's Hospital Research Institute, and Department of Biochemistry and Molecular Biology Calgary, University of Calgary, Alberta T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-6270","authenticated-orcid":false,"given":"Savraj","family":"Grewal","sequence":"additional","affiliation":[{"name":"Clark H Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, Alberta Children's Hospital Research Institute, and Department of Biochemistry and Molecular Biology Calgary, University of Calgary, Alberta T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042701013169000_JEB226027C1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1159\/000052764","article-title":"Prenatal exposure to a maternal low protein diet shortens life span in rats","volume":"47","author":"Aihie Sayer","year":"2001","journal-title":"Gerontology"},{"key":"2021042701013169000_JEB226027C2","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.cmet.2007.09.002","article-title":"Diabetic larvae and obese flies-emerging studies of metabolism in Drosophila","volume":"6","author":"Baker","year":"2007","journal-title":"Cell Metab."},{"key":"2021042701013169000_JEB226027C3","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1534\/genetics.120.303219","article-title":"Tolerance to hypoxia is promoted by FOXO regulation of the innate immunity transcription factor NF-kappaB\/Relish in Drosophila","volume":"215","author":"Barretto","year":"2020","journal-title":"Genetics"},{"key":"2021042701013169000_JEB226027C4","doi-asserted-by":"publisher","first-page":"e26952","DOI":"10.7554\/eLife.26952","article-title":"PGAM5 promotes lasting FoxO activation after developmental mitochondrial stress and extends lifespan in Drosophila","volume":"6","author":"Borch Jensen","year":"2017","journal-title":"eLife"},{"key":"2021042701013169000_JEB226027C5","doi-asserted-by":"publisher","first-page":"648","DOI":"10.3945\/jn.109.111179","article-title":"The developmental origins, mechanisms, and implications of metabolic syndrome","volume":"140","author":"Bruce","year":"2010","journal-title":"J. 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