{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T07:39:50Z","timestamp":1792568390818,"version":"4.5.0"},"reference-count":60,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS\u20102024\u201000438349"],"award-info":[{"award-number":["RS\u20102024\u201000438349"]}],"id":[{"id":"10.13039\/501100003710","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":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nicotinamide adenine dinucleotide (NAD\n                    <jats:sup>+<\/jats:sup>\n                    ) is an essential metabolite that regulates diverse cellular metabolic processes. Primary cilia, hair\u2013like organelles on the cell surface, function as critical signaling hubs. Here, we demonstrate that cellular NAD\n                    <jats:sup>+<\/jats:sup>\n                    levels are key regulators of both primary cilia growth and lysosomal function in hypothalamic neurons. NAD\n                    <jats:sup>+<\/jats:sup>\n                    depletion induces ciliary shortening and diminishes lysosomal activity in a cilia\u2013dependent manner. Mechanistically, the lysosomal repair complex protein CHMP4B translocates from periciliary satellites to lysosomes during lysosomal stress, a process impaired by ciliary dysgenesis. Disrupted lysosomal recruitment of CHMP4B leads to abnormal lysosomal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and lysosomal dysfunction. Aged mice with hypothalamic NAD\n                    <jats:sup>+<\/jats:sup>\n                    deficiency exhibit shortened cilia and lysosomal stress phenotypes, both of which are restored by calorie restriction (CR). Moreover, CR improves aging\u2013associated metabolic dysfunction, at least in part, through hypothalamic cilia\u2013dependent mechanisms. These findings identify a primary cilium\u2013mediated\u2013NAD\n                    <jats:sup>+<\/jats:sup>\n                    signaling axis that maintains lysosomal homeostasis in hypothalamic neurons, the disruption of which drives metabolic aging.\n                  <\/jats:p>","DOI":"10.1111\/acel.70745","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:54:13Z","timestamp":1792565653000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Cilia\u2013Centered Nicotinamide Adenine Dinucleotide (\n                    <scp>NAD<\/scp>\n                    <sup>+<\/sup>\n                    ) Signaling Network Regulates Hypothalamic Lysosomal Homeostasis and Metabolic Aging"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5222-2413","authenticated-orcid":false,"given":"Se Eun","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-5006","authenticated-orcid":false,"given":"Eun","family":"Roh","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Boramae Medical Center Seoul National University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6306-7443","authenticated-orcid":false,"given":"Jae Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Yeon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae Beom","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3345-7191","authenticated-orcid":false,"given":"Hyo Sun","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4482-3920","authenticated-orcid":false,"given":"Mun Gyeom","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young In","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wontae","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Ulsan College of Medicine  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