{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:40:07Z","timestamp":1792813207986,"version":"4.5.0"},"reference-count":58,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["SELECTHAPLOID 101001341"],"award-info":[{"award-number":["SELECTHAPLOID 101001341"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000270","name":"Natural Environment Research Council","doi-asserted-by":"publisher","award":["NE\/W001020\/1"],"award-info":[{"award-number":["NE\/W001020\/1"]}],"id":[{"id":"10.13039\/501100000270","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["IZCO\u20100\u2010240511"],"award-info":[{"award-number":["IZCO\u20100\u2010240511"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Genetic trade\u2010offs can constrain life\u2010history evolution resulting in the evolution of ageing. Reduced insulin\/insulin\u2010like signalling (rIIS) improves somatic maintenance and dramatically increases lifespan in\n \n Caenorhabditis elegans<\/jats:italic>\n <\/jats:styled-content>\n , but the effects on fitness are unclear. Here we used a novel experimental approach to show that, contrary to the prevailing paradigm, rIIS via\n daf\u20102<\/jats:italic>\n RNAi during development can improve development, reproduction, survival, individual fitness, and population growth rate in the laboratory and semi\u2010natural conditions. However, developmental rIIS extends lifespan and improves fitness only in some temperatures, which explains why our results differ from previous findings. Furthermore, while developmental rIIS can improve a suite of life\u2010history traits in parents, it slows down offspring development. Finally, because rIIS interferes with environmental sensing and compromises adaptive developmental plasticity in response to stress, a central part of\n \n C. elegans<\/jats:italic>\n <\/jats:styled-content>\n life history in nature, the ability to sense the environment correctly during development comes at the cost of accelerated senescence. These results suggest the complexity of gene\u2010by\u2010environment interactions during development imposes constraints on molecular signalling networks leading to genetic trade\u2010offs across the life course that natural selection in late\u2010life is unable to resolve. However, these constraints can be resolved by artificially fine\u2010tuning gene expression at different ages.\n <\/jats:p>","DOI":"10.1111\/acel.70783","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:41:41Z","timestamp":1792809701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Live Fast, Die Old: Lowering Insulin Signalling During Development Can Speed Growth, Increase Reproduction and Lifespan, but Impair Environmental Sensing and Harm Offspring in\n Caenorhabditis elegans<\/i>"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6824-3445","authenticated-orcid":false,"given":"Sara D.","family":"Irish","sequence":"first","affiliation":[{"name":"School of Biological Sciences University of East Anglia, Norwich Research Park Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel","family":"Kimberley","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of East Anglia, Norwich Research Park Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6811-0762","authenticated-orcid":false,"given":"Peter","family":"Lenart","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Carlsson","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of East Anglia, Norwich Research Park Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6204-6752","authenticated-orcid":false,"given":"Anna","family":"Braybrooke","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of East Anglia, Norwich Research Park Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-1257","authenticated-orcid":false,"given":"Benjamin","family":"Towbin","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1234-935X","authenticated-orcid":false,"given":"Simone","family":"Immler","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of East Anglia, Norwich Research Park Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5809-1203","authenticated-orcid":false,"given":"Alexei A.","family":"Maklakov","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of East Anglia, Norwich Research Park Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.devcel.2017.07.002","article-title":"The Helicase Aquarius\/EMB\u20104 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription","volume":"42","author":"Akay A.","year":"2017","journal-title":"Developmental Cell"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"E15","DOI":"10.1086\/663194","article-title":"The Forms and Fitness Cost of Senescence: Age\u2010Specific Recapture, Survival, Reproduction, and Reproductive Value in a Wild Bird Population","volume":"179","author":"Bouwhuis S.","year":"2012","journal-title":"American Naturalist"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.exger.2015.09.002","article-title":"What Can Long\u2010Lived Mutants Tell Us About Mechanisms Causing Aging and Lifespan Variation in Natural Environments?","volume":"71","author":"Briga M.","year":"2015","journal-title":"Experimental Gerontology"},{"key":"e_1_2_10_5_1","first-page":"378","article-title":"glmmTMB Balances Speed and Flexibility Among Packages for Zero\u2010Inflated Generalized Linear Mixed Modeling","volume":"9","author":"Brooks M. 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