Storage Protein-Mediated Translation Control Links Juvenile Diet to Longevity in Drosophila

Storage Protein-Mediated Translation Control Links Juvenile Diet to Longevity in Drosophila | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Biological Sciences - Article Storage Protein-Mediated Translation Control Links Juvenile Diet to Longevity in Drosophila Fumiaki Obata, Hina Kosakamoto, Rina Okada, Clive Barker, Jun Seita, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6791339/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Dietary restriction (DR), whether applied during adulthood or juvenile stages, extends lifespan across diverse species. However, the mechanisms by which early-life dietary interventions influence adult physiology and longevity remain poorly understood. Here, using Drosophila as a model, we demonstrate that protein restriction during the larval stage (early-life protein restriction, ePR) promotes adult lifespan by reducing storage protein levels. Stable isotope tracing reveals that dietary amino acids obtained in the larval stage are retained into adulthood, especially incorporated into ribosomal proteins. This is mediated by larval serum protein 2 (Lsp2), a major storage protein, whose expression is durably downregulated by ePR. Both dietary (ePR) and genetic (Lsp2-RNAi) reduction of the protein storage lead to decreased ribosomal protein levels and translation activity in early adulthood. Notably, these storage proteins are enriched in aromatic amino acids such as tyrosine, and larval tyrosine restriction alone is sufficient to suppress translation and promote longevity. These findings show that storage proteins mediate the effect of larval nutrition on adult longevity via controlling translation. Our study uncovers a previously unrecognised mechanism of nutritional memory that links early-life diet to life-long organismal health. Biological sciences/Physiology/Ageing Biological sciences/Molecular biology/Translation/Ribosome Biological sciences/Physiology/Metabolism/Homeostasis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTable1proteome.xlsx Supplementary Table 1 SupplementaryTable21.xlsx Supplementary Table 2 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6791339","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":485010153,"identity":"74c75d1c-df2e-4dc3-81dd-3247a73bf121","order_by":0,"name":"Fumiaki 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However, the mechanisms by which early-life dietary interventions influence adult physiology and longevity remain poorly understood. Here, using Drosophila as a model, we demonstrate that protein restriction during the larval stage (early-life protein restriction, ePR) promotes adult lifespan by reducing storage protein levels. Stable isotope tracing reveals that dietary amino acids obtained in the larval stage are retained into adulthood, especially incorporated into ribosomal proteins. This is mediated by larval serum protein 2 (Lsp2), a major storage protein, whose expression is durably downregulated by ePR. Both dietary (ePR) and genetic (Lsp2-RNAi) reduction of the protein storage lead to decreased ribosomal protein levels and translation activity in early adulthood. Notably, these storage proteins are enriched in aromatic amino acids such as tyrosine, and larval tyrosine restriction alone is sufficient to suppress translation and promote longevity. 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