{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:41:15Z","timestamp":1793400075434,"version":"4.5.0"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is characterized by the progressive loss of dopaminergic neurons, with growing evidence underscoring the critical role of immunosenescence\u2014the age-related dysregulation of the immune system\u2014in its pathogenesis. This review delineates the intricate interplay between systemic immunosenescence, chronic neuroinflammation, and neurodegeneration in PD. We explore how age-related remodeling of the peripheral immune system, termed \u201cinflammaging,\u201d promotes a pro-inflammatory milieu that compromises blood-brain barrier integrity and drives microglial activation within the central nervous system. A central focus is the senescence-associated secretory phenotype, a cocktail of pro-inflammatory factors released by senescent glial cells, which perpetuates a self-sustaining cycle of neuroinflammation, facilitates the propagation of pathological \u03b1-synuclein, and ultimately accelerates neuronal loss. The review further examines the disruption of vital neuroimmune communication pathways, including aberrant neuron-glia and gut-brain axis signaling, which are corrupted in the aging brain. We evaluate the translational promise of emerging therapeutic strategies designed to target this immunosenescence-neuroinflammation axis. These include senolytic agents to clear senescent cells, adoptive regulatory T-cell therapy, cytokine-targeted immunomodulation, and immune rejuvenation approaches. Finally, we discuss significant translational challenges and outline future research directions, emphasizing the need for advanced model systems, biomarker development, and AI-driven personalized medicine to successfully develop disease-modifying immunotherapies that disrupt the vicious cycle of immunosenescence and neurodegeneration in PD.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1749278","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T05:23:07Z","timestamp":1770873787000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunosenescence and inflammaging in Parkinson\u2019s disease: mechanisms and therapeutic prospects"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruyu","family":"Yan","sequence":"first","affiliation":[{"name":"Queen Mary School, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Feng","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.336138","article-title":"From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"17","author":"Wakhloo","year":"2022","journal-title":"Neural Regener 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