{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:34:31Z","timestamp":1785411271192,"version":"3.56.0"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG91b"],"award-info":[{"award-number":["DFG91b"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Microglia, the brain's resident immune cells, are crucial for maintaining healthy brain homeostasis. However, as the brain ages, microglia can shift from a neuroprotective to a neurotoxic phenotype, contributing to chronic inflammation and promoting neurodegenerative processes. Despite the importance of understanding microglial aging, there are currently few human in\u00a0vitro models to study these processes. To address this gap, we have developed a model in which human microglia undergo accelerated aging through inducible progerin expression. HMC3\u2010Progerin cells display key age\u2010related markers such as activation of the senescence\u2010associated secretory phenotype (SASP) as well as an increase in DNA damage. These prematurely aged HMC3 cells show a reduced response to LPS activation, exhibit impairments in essential microglial functions including decreased migration and phagocytosis as well as transcriptomic alterations including a shift observed in aging and neurodegeneration. Additionally, we observed an impaired stress response and a defect in nucleocytoplasmic transport, especially affecting the amyotrophic lateral sclerosis (ALS) associated protein FUS. This suggests that microglia play a contributory role in driving neurodegenerative processes in the aging brain. Our microglia aging model offers a valuable tool for exploring how aged microglia affect brain function, enhancing our understanding of their role in brain aging.<\/jats:p>","DOI":"10.1111\/acel.70232","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T11:01:54Z","timestamp":1758279714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prematurely Aged Human Microglia Exhibit Impaired Stress Response and Defective Nucleocytoplasmic Shuttling of\n                    <scp>ALS<\/scp>\n                    Associated\n                    <scp>FUS<\/scp>"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8699-0794","authenticated-orcid":false,"given":"Christiane","family":"Hartmann","sequence":"first","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht Kossel\u201d, Department of Neurology Rostock University Medical Center  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