{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:52:46Z","timestamp":1768510366426,"version":"3.49.0"},"posted":{"date-parts":[[2024,2,8]]},"group-title":"Molecular Biology","reference-count":56,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Dietary restriction (DR) mitigates loss of proteostasis associated with aging that underlies neurodegenerative conditions including Alzheimer\u2019s disease and related dementias. Previously, we observed increased translational efficiency of certain FMRFamide-like neuropeptide (\n                  <jats:italic>flp<\/jats:italic>\n                  ) genes and the neuroprotective growth factor progranulin gene\n                  <jats:italic>prgn-1<\/jats:italic>\n                  under dietary restriction in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  . Here, we tested the effects of\n                  <jats:italic>flp-5<\/jats:italic>\n                  ,\n                  <jats:italic>flp-14<\/jats:italic>\n                  ,\n                  <jats:italic>flp-15<\/jats:italic>\n                  and\n                  <jats:italic>pgrn-1<\/jats:italic>\n                  on lifespan and proteostasis under both standard and dietary restriction conditions. We also tested and distinguished function based on their expression in either neuronal or non-neuronal tissue. Lowering the expression of\n                  <jats:italic>pgrn-1<\/jats:italic>\n                  and\n                  <jats:italic>flp<\/jats:italic>\n                  genes selectively in neural tissue showed no difference in survival under normal feeding conditions nor under DR in two out of three experiments performed. Reduced expression of\n                  <jats:italic>flp-14<\/jats:italic>\n                  in non-neuronal tissue showed decreased lifespan that was not specific to DR. With respect to proteostasis, a genetic model of DR from mutation of the\n                  <jats:italic>eat-2<\/jats:italic>\n                  gene that showed increased thermotolerance compared to fully fed wild type animals demonstrated no change in thermotolerance in response to knockdown of\n                  <jats:italic>pgrn-1<\/jats:italic>\n                  or\n                  <jats:italic>flp<\/jats:italic>\n                  genes. Finally, we tested effects on motility in a neural-specific model of proteotoxicity and found that neuronal knockdown of\n                  <jats:italic>pgrn-1<\/jats:italic>\n                  and\n                  <jats:italic>flp<\/jats:italic>\n                  genes improved motility in early life regardless of diet. However, knocking these genes down in non-neuronal tissue had variable results. RNAi targeting\n                  <jats:italic>flp-14<\/jats:italic>\n                  increased motility by day seven of adulthood regardless of diet. Interestingly, non-neuronal RNAi of\n                  <jats:italic>pgrn-1<\/jats:italic>\n                  decreased motility under standard feeding conditions while DR increased motility for this gene knockdown by day seven (early mid-life). Results show that\n                  <jats:italic>pgrn-1<\/jats:italic>\n                  ,\n                  <jats:italic>flp-5<\/jats:italic>\n                  ,\n                  <jats:italic>flp-14<\/jats:italic>\n                  , and\n                  <jats:italic>flp-15<\/jats:italic>\n                  do not have major roles in diet-related changes in longevity or whole-body proteostasis. However, reduced expression of these genes in neurons increases motility early in life in a neural-specific model of proteotoxicity, whereas knockdown of non-neuronal expression mostly increases motility in mid-life under the same conditions.\n                <\/jats:p>","DOI":"10.1101\/2024.02.06.579250","type":"posted-content","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T21:21:37Z","timestamp":1707427297000},"source":"Crossref","is-referenced-by-count":1,"title":["Roles of progranulin and FRamides in neural versus non-neural tissues on dietary restriction-related longevity and proteostasis in\n                  <i>C. elegans<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-3093","authenticated-orcid":false,"given":"Dilawar Ahmad","family":"Mir","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8829-9999","authenticated-orcid":false,"given":"Matthew","family":"Cox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan","family":"Horrocks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengxin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aric","family":"Rogers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024021212101521000_2024.02.06.579250v1.1","doi-asserted-by":"crossref","first-page":"1075215","DOI":"10.3389\/fcell.2023.1075215","article-title":"Dysregulated proteostasis network in neuronal diseases","volume":"11","year":"2023","journal-title":"Front. 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