{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:21:08Z","timestamp":1789730468278,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In Hutchinson\u2010Gilford progeria syndrome (HGPS), dysfunctional autophagy results in the accumulation of progerin, a lamin A mutant variant that alters a plethora of processes, inducing senescence and driving premature aging. Therefore, the elimination of progerin through autophagy restoration emerges as a therapeutic intervention against HGPS. However, a comprehensive study of autophagy flux in HGPS remains to be addressed. In this study, the dynamics of autophagy in HGPS fibroblasts were analyzed utilizing different HGPS cell models and experimental approaches. The autophagy\u2010associated transcriptomic profile was determined, and the autophagy\u2010lysosome axis was comprehensively analyzed. We demonstrated that progerin induces the formation of autophagosomes but impairs their maturation and subsequent fusion with lysosomes. This alteration is attributed in part to the progerin\u2010mediated decreased expression of STX17, a marker of mature autophagosomes, and LAMP1, a membrane lysosomal protein, as well as the presence of defective lysosomes. In line with this, the rescue of STX17 and LAMP1 expression improved autophagy flux. Interestingly, treatment of HGPS fibroblasts with Selinexor, an autophagy activator, elicited nuclear accumulation of TFEB and enhanced lysosomal biogenesis and function, thereby activating autophagy. Selinexor treatment improved both autophagosome maturation and autophagosome\u2010lysosome fusion, which ultimately led to effective autophagic degradation of progerin. In summary, progerin impedes proper autophagy flux, thus preventing its own autophagic degradation, which underscores the relevance of targeting the autophagy\u2010lysosome pathway to counteract the toxic accumulation of progerin.<\/jats:p>","DOI":"10.1111\/acel.70649","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:47:27Z","timestamp":1785336447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Progerin Hinders Autophagy Flux at Its Final Stages in Hutchinson\u2010Gilford Progeria Syndrome Cells, Preventing Its Own Autophagic Degradation"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3903-1467","authenticated-orcid":false,"given":"Ian","family":"Garc\u00eda\u2010Aguirre","sequence":"first","affiliation":[{"name":"Departamento de Bioingenier\u00eda Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas Alejandro","family":"Reyes\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica y Biolog\u00eda Molecular Centro de Investigaci\u00f3n y de Estudios Avanzados  Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Unzueta","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica y Biolog\u00eda Molecular Centro de Investigaci\u00f3n y de Estudios Avanzados  Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Guevara\u2010Namorado","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica y Biolog\u00eda Molecular Centro de Investigaci\u00f3n y de Estudios Avanzados  Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4546-5863","authenticated-orcid":false,"given":"Solangy","family":"Lizcano\u2010Meneses","sequence":"additional","affiliation":[{"name":"Departamento de Bioingenier\u00eda Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey  Ciudad de M\u00e9xico Mexico"},{"name":"Department of Cell Biology Center for Research and Advanced Studies of the National Polytechnic Institute  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Gonzalo","sequence":"additional","affiliation":[{"name":"Edward A. Doisy Department of Biochemistry and Molecular Biology Saint Louis University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Baldan","sequence":"additional","affiliation":[{"name":"Edward A. 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