{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:41:43Z","timestamp":1788846103681,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T00:00:00Z","timestamp":1536278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"L'Or\u00e9al Research and Innovation Center"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Plant extracts containing salicylates are probably the most ancient remedies to reduce fever and ease aches of all kind. Recently, it has been shown that salicylates activate adenosine monophosphate\u2010activated kinase (AMPK), which is now considered as a promising target to slow down aging and prevent age\u2010related diseases in humans. Beneficial effects of AMPK activation on lifespan have been discovered in the model organism <jats:italic>Caenorhabditis elegans <\/jats:italic>(<jats:italic>C.\u00a0elegans<\/jats:italic>). Indeed, salicylic acid and acetylsalicylic acid extend lifespan in worms by activating AMPK and the forkhead transcription factor DAF\u201016\/FOXO. Here, we investigated whether another salicylic acid derivative 5\u2010octanoyl salicylic acid (C8\u2010SA), developed as a controlled skin exfoliating ingredient, had similar properties using <jats:italic>C. elegans<\/jats:italic> as a model. We show that C8\u2010SA increases lifespan of <jats:italic>C. elegans<\/jats:italic> and that a variety of pathways and genes are required for C8\u2010SA\u2010mediated lifespan extension. C8\u2010SA activates AMPK and inhibits TOR both in nematodes and in primary human keratinocytes. We also show that C8\u2010SA can induce both autophagy and the mitochondrial unfolded protein response (UPR<jats:sup>mit<\/jats:sup>) in nematodes. This induction of both processes is fully required for lifespan extension in the worm. In addition, we found that the activation of autophagy by C8\u2010SA fails to occur in worms with compromised UPR<jats:sup>mit<\/jats:sup>, suggesting a mechanistic link between these two processes. Mutants that are defective in the mitochondrial unfolded protein response exhibit constitutive high autophagy levels. Taken together, these data therefore suggest that C8\u2010SA positively impacts longevity in worms through induction of autophagy and the UPR<jats:sup>mit<\/jats:sup>.<\/jats:p>","DOI":"10.1111\/acel.12830","type":"journal-article","created":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T10:29:56Z","timestamp":1536316196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A salicylic acid derivative extends the lifespan of <i>Caenorhabditis elegans<\/i> by activating autophagy and the mitochondrial unfolded protein response"],"prefix":"10.1111","volume":"17","author":[{"given":"Mehrnaz","family":"Shamalnasab","sequence":"first","affiliation":[{"name":"IGFL, UMR5262 Ecole Normale Sup\u00e9rieure de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon\u2010Pierre","family":"Gravel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry McGill University Montreal Quebec Canada"},{"name":"Goodman Cancer Research Centre McGill University Montreal Quebec Canada"},{"name":"Facult\u00e9 de pharmacie Universit\u00e9 de Montr\u00e9al Montr\u00e9al Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"St\u2010Pierre","sequence":"additional","affiliation":[{"name":"Department of Biochemistry McGill University Montreal Quebec Canada"},{"name":"Goodman Cancer Research Centre McGill University Montreal Quebec Canada"},{"name":"Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Breton","sequence":"additional","affiliation":[{"name":"L\u2019Or\u00e9al Research &amp; Innovation Aulnay\u2010sous\u2010Bois France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"L\u2019Or\u00e9al Research &amp; Innovation Aulnay\u2010sous\u2010Bois France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Aguilaniu","sequence":"additional","affiliation":[{"name":"Instituto Serrapilheira Rio de Janeiro Brazil"},{"name":"D\u00e9tach\u00e9 from CNRS (section 24) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080418"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065768"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4151"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006695"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05904"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26952"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00580.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5118"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077780"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.12.016"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00071-5"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.08.047"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1215327"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004860"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12188"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/20694"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.090738"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08980"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3267"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1056"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2006.00241.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9330"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12338"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/10.1.63"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05837"},{"key":"e_1_2_6_27_1","unstructured":"Pedersen J. 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