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However, aging is a heterogeneous process and individual organisms age differently. Moreover, within the same organism, cells or organs do not age at the same time or speed. For instance, although neurodegeneration is a key trait of aging, neurological symptoms normally manifest long after multiple indicators of aging in peripheral tissues. The genetic determinants of aging remain poorly understood. Mutations in leucine-rich repeat kinase 2 (LRRK2) are major genetic risk factors for Parkinson\u2019s disease (PD). By analyzing PD patients and mice with LRRK2 gain of function mutation (LRRK2\n                  <jats:sup>GoF<\/jats:sup>\n                  ), we demonstrate that PD is an accelerated aging disease characterized by systemic low-grade STING-dependent inflammation (inflammaging) that first manifests in the periphery then disrupts the blood brain barrier and progresses to the brain resulting in neurodegeneration. Mechanistically, we demonstrate that a primary consequence of aging or\n                  <jats:italic>\n                    Lrrk2\n                    <jats:sup>GoF<\/jats:sup>\n                  <\/jats:italic>\n                  is endolysosomal decline. This results in the cytosolic build-up of extraneous self-DNA and subsequent shedding of DNA-containing extracellular vesicles thereby triggering the cGAS- STING pathway cell-intrinsically and intercellularly in distant host cells. This study unveils the cGAS-STING pathway and LRRK2\n                  <jats:sup>GoF<\/jats:sup>\n                  as key determinants and potential targets for preventive or therapeutic strategies against accelerated aging, inflammaging and neurodegeneration.\n                <\/jats:p>","DOI":"10.64898\/2026.03.15.711864","type":"posted-content","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:25:16Z","timestamp":1773822316000},"source":"Crossref","is-referenced-by-count":0,"title":["Aging-associated endolysosomal decline drives inflammaging and neurodegeneration through the STING-IFN-I axis"],"prefix":"10.64898","author":[{"given":"Maria","family":"\u00d6berg","sequence":"first","affiliation":[{"name":"Institute of Biomedicine, Department of Microbiology and Immunology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Maric","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneli","family":"Str\u00f6mberg","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Department of Microbiology and Immunology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn","family":"Myers","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Department of Microbiology and Immunology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najmeh","family":"Saffarzadeh","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Department of Microbiology and Immunology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Fabrikova","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Department of Microbiology and Immunology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Fabrik","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Department of Microbiology and Immunology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Rivas-Galvez","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Department of Microbiology and Immunology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina P","family":"Skibicka","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Nutritional Sciences, Pennsylvania State University, State College, PA, United States"},{"name":"Huck Institutes of the Life Sciences, Pennsylvania State University, State College, PA, United State"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"Kurzawa-Akanbi","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesine","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden;"},{"name":"Department of Neurology, Skanes University Hospital, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson O.","family":"Gekara","sequence":"additional","affiliation":[{"name":"Wenner-Gren Institute, University of Stockholm, Stockholm, Sweden"},{"name":"Institute of Medical Microbiology and Hygiene, Medical Center - 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