{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:45:05Z","timestamp":1792611905684,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470877"],"award-info":[{"award-number":["32470877"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401817"],"award-info":[{"award-number":["82401817"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82603057"],"award-info":[{"award-number":["82603057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lysosomal decline and proteostasis collapse are defining features of aging and major contributors to neurodegenerative vulnerability, yet interventions that preserve neuronal lysosomal function across aging remain poorly defined. Here, we identify 20(S)\u2010ginsenoside Rg3, a ginseng\u2010derived natural product, as a geroprotective small molecule in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    <\/jats:styled-content>\n                    . Rg3 extended lifespan and preserved key physiological outputs, including locomotion and pharyngeal pumping, indicating that Rg3 delays functional aging. Rg3 also maintained mechanosensory neuron integrity and touch sensitivity, suppressed neuronal polyglutamine aggregation, and protected dopaminergic neurons against \u03b1\u2010synuclein\u2010induced degeneration. At the cellular level, Rg3 restored age\u2010impaired lysosomal function and autophagic flux in neurons. Mechanistically, Rg3 shifted neuronal phosphoinositide reporter signatures toward a PI(4)P\u2010enriched and PI(3)P\u2010reduced state, consistent with signaling lipid remodeling at lysosomal membranes. This phosphoinositide shift coincided with reduced RSKS\u20101\/S6K phosphorylation, indicating suppression of TOR complex 1 (TORC1), and promoted nuclear localization of HLH\u201030, the\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>C. elegans<\/jats:italic>\n                    <\/jats:styled-content>\n                    ortholog of transcription factor EB (TFEB), thereby engaging a conserved lysosomal program. Collectively, these results define Rg3 as a natural\u2010product geroprotector that couples lysosomal lipid remodeling to TORC1\u2013HLH\u201030 signaling to preserve lysosomal competence, neuronal proteostasis, and organismal fitness during aging. Our study nominates phosphoinositide control of lysosomal identity as a therapeutic entry point for healthy aging and neuroprotection.\n                  <\/jats:p>","DOI":"10.1111\/acel.70755","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:26:01Z","timestamp":1791642361000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside Rg3 Promotes Healthy Aging Through Phosphoinositide\u2010Associated Lysosomal Regulation in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1111","volume":"25","author":[{"given":"Haiyang","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0116-2493","authenticated-orcid":false,"given":"Shiming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5416-932X","authenticated-orcid":false,"given":"Yaoyong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"},{"name":"College of Food Science Fujian Agriculture and Forestry University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sirio Pharma Co., Ltd  Shantou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longnong","family":"You","sequence":"additional","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9657-6225","authenticated-orcid":false,"given":"Kuncan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Jinshan Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5754-1498","authenticated-orcid":false,"given":"Jinhong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Gan","sequence":"additional","affiliation":[{"name":"Sirio Pharma Co., Ltd  Shantou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiane\u2010Kang","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3350-8498","authenticated-orcid":false,"given":"Lingjun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Food Science and Engineering, School of Agriculture and Biology Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1255404"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010019\u20100185\u20104"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.117.204222"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.042"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/77.1.71"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1097\u20102765(00)80125\u20102"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18459"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010400"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05185"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.09.027"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.7.1783"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyab004"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5464\u201009.2010"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0040024"},{"issue":"5","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1002\/dvdy.22231","article-title":"C. elegans\n                   as a Model Organism to Investigate Molecular Pathways Involved With Parkinson's Disease","volume":"239","author":"Harrington A. J.","year":"2010","journal-title":"Developmental Dynamics: An Official Publication of the American Association of the Anatomists"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/20694"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002165"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/366461a0"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2016.08.004"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1713645"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.074047"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14459"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3267"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.10181"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.12.001"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1319"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2024.2355008"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087782"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3232"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00757-5"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114138"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202403058"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2014.01.004"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4132"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2718"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.32"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2302801120"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55745"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.05.057"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-018-09449-1"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113865"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1fo00576f"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.975784"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adc9236"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1207056"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70755","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70755","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70755","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:20:18Z","timestamp":1792610418000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/acel.70755"],"URL":"https:\/\/doi.org\/10.1111\/acel.70755","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70755"}}