{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:18:20Z","timestamp":1792034300064,"version":"4.4.0"},"reference-count":327,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031478","name":"Next Generation EU","doi-asserted-by":"crossref","award":["DM 155711.10.2022"],"award-info":[{"award-number":["DM 155711.10.2022"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Aging is accompanied by profound alterations in immune function, termed immunosenescence, and by a chronic, low-grade inflammatory state known as inflammaging. These processes are increasingly recognized as central drivers of age-related neurodegenerative diseases, including Alzheimer\u2019s Disease, Parkinson\u2019s Disease, Amyotrophic Lateral Sclerosis and Multiple Sclerosis. In the central nervous system, senescent microglia and astrocytes lose their homeostatic and neuroprotective functions, while systemic immune aging and blood\u2013brain barrier dysfunction further amplify neuroinflammation and impair protein aggregate clearance. This sustained pro-inflammatory environment promotes synaptic dysfunction, neuronal loss and cognitive decline. Here, we synthesize current knowledge of the mechanistic links among immunosenescence, inflammaging, and neurodegeneration, highlighting innate and adaptive immune dysregulation, mitochondrial impairment, and failed resolution pathways. We further discuss emerging therapeutic strategies, including senolytics, immunoceuticals, microbiome-based interventions and advanced drug delivery systems, aimed at restoring immune homeostasis and enhancing brain resilience. By integrating mechanistic and translational insights, this review provides a framework for developing novel interventions to target immune aging in neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/cells15080657","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T15:26:39Z","timestamp":1775661999000},"page":"657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2889-2150","authenticated-orcid":false,"given":"Gianmarco","family":"Bertoni","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9967-8050","authenticated-orcid":false,"given":"Sara","family":"Ristori","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-8123","authenticated-orcid":false,"given":"Daniela","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/acschemneuro.3c00531","article-title":"Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement","volume":"15","author":"Tenchov","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Aiello, A., Farzaneh, F., Candore, G., Caruso, C., Davinelli, S., Gambino, C.M., Ligotti, M.E., Zareian, N., and Accardi, G. (2019). Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02247"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-981-13-3681-2_2","article-title":"The Immune System and Its Dysregulation with Aging","volume":"91","author":"Pawelec","year":"2019","journal-title":"Subcell. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fulop, T., Larbi, A., Dupuis, G., Le Page, A., Frost, E.H., Cohen, A.A., Witkowski, J.M., and Franceschi, C. (2018). Immunosenescence and Inflamm-Aging as Two Sides of the Same Coin: Friends or Foes?. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01960"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7123","DOI":"10.1111\/febs.15770","article-title":"Hallmarks of the Aging T-Cell System","volume":"288","author":"Zhang","year":"2021","journal-title":"FEBS J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s10522-015-9563-2","article-title":"Impact of Age, Sex and CMV-Infection on Peripheral T Cell Phenotypes: Results from the Berlin BASE-II Study","volume":"16","author":"Derhovanessian","year":"2015","journal-title":"Biogerontology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00005-015-0377-3","article-title":"Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity","volume":"64","author":"Minciullo","year":"2016","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cytogfr.2024.08.004","article-title":"Inflamm-Ageing: How Cytokines and Nutrition Shape the Trajectory of Ageing","volume":"82","author":"Coperchini","year":"2025","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s40035-025-00517-1","article-title":"Immunosenescence in Aging and Neurodegenerative Diseases: Evidence, Key Hallmarks, and Therapeutic Implications","volume":"14","author":"Chen","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wrona, M.V., Ghosh, R., Coll, K., Chun, C., and Yousefzadeh, M.J. (2024). The 3 I\u2019s of Immunity and Aging: Immunosenescence, Inflammaging, and Immune Resilience. Front. Aging, 5.","DOI":"10.3389\/fragi.2024.1490302"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1126\/science.aag2638","article-title":"Multifaceted Interactions between Adaptive Immunity and the Central Nervous System","volume":"353","author":"Kipnis","year":"2016","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41583-020-0263-9","article-title":"Immune Cell Regulation of Glia during CNS Injury and Disease","volume":"21","author":"Greenhalgh","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.cell.2018.05.003","article-title":"Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration","volume":"173","author":"Deczkowska","year":"2018","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic Inflammation in the Etiology of Disease across the Life Span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41392-023-01451-2","article-title":"Immunosenescence: Molecular Mechanisms and Diseases","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., and Di Benedetto, S. (2025). Immunosenescence and Inflammaging: Mechanisms and Modulation through Diet and Lifestyle. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1708280"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"111357","DOI":"10.1016\/j.mad.2020.111357","article-title":"The Conundrum of Human Immune System \u201cSenescence\u201d","volume":"192","author":"Pawelec","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: A New Immune\u2013Metabolic Viewpoint for Age-Related Diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression","volume":"5","author":"Desprez","year":"2010","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Copp\u00e9, J.P., Patil, C.K., Rodier, F., Sun, Y., Mu\u00f1oz, D.P., Goldstein, J., Nelson, P.S., Desprez, P.Y., and Campisi, J. (2008). Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the P53 Tumor Suppressor. PLoS Biol., 6.","DOI":"10.1371\/journal.pbio.0060301"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging: An Evolutionary Perspective on Immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Franceschi, C., Garagnani, P., Morsiani, C., Conte, M., Santoro, A., Grignolio, A., Monti, D., Capri, M., and Salvioli, S. (2018). The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00061"},{"key":"ref_23","first-page":"1675","article-title":"Immune System, Cell Senescence, Aging and Longevity\u2014Inflamm-Aging Reappraised","volume":"19","author":"Salvioli","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1093\/gerona\/glu057","article-title":"Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases","volume":"69","author":"Franceschi","year":"2014","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1159\/000156466","article-title":"Immunosenescence and Immunogenetics of Human Longevity","volume":"15","author":"Ostan","year":"2008","journal-title":"Neuroimmunomodulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.15252\/embr.201439245","article-title":"Senescence and Apoptosis: Dueling or Complementary Cell Fates?","volume":"15","author":"Childs","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e158450","DOI":"10.1172\/JCI158450","article-title":"Cellular Senescence: A Key Therapeutic Target in Aging and Diseases","volume":"132","author":"Zhang","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular Senescence: When Bad Things Happen to Good Cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.celrep.2011.11.005","article-title":"The NLRP3 Inflammasome Promotes Age-Related Thymic Demise and Immunosenescence","volume":"1","author":"Youm","year":"2012","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s41586-023-06373-1","article-title":"CGAS\u2013STING Drives Ageing-Related Inflammation and Neurodegeneration","volume":"620","author":"Gulen","year":"2023","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s43587-023-00399-w","article-title":"CISH Impairs Lysosomal Function in Activated T Cells Resulting in Mitochondrial DNA Release and Inflammaging","volume":"3","author":"Jin","year":"2023","journal-title":"Nat. Aging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4172\/2155-9562.1000209","article-title":"T-Lymphocyte Deficiency Exacerbates Behavioral Deficits in the 6-OHDA Unilateral Lesion Rat Model for Parkinson\u2019s Disease","volume":"5","author":"Wheeler","year":"2014","journal-title":"J. Neurol. Neurophysiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1159\/000323779","article-title":"Serum Levels of Chemokines in Parkinson\u2019s Disease","volume":"18","author":"Scalzo","year":"2011","journal-title":"Neuroimmunomodulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1212\/WNL.57.6.952","article-title":"Marked Increase in Cyclooxygenase-2 in ALS Spinal Cord Implications for Therapy","volume":"57","author":"Yasojima","year":"2001","journal-title":"Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0165-5728(01)00496-9","article-title":"Occurrence of T Cells in the Brain of Alzheimer\u2019s Disease and Other Neurological Diseases","volume":"124","author":"Togo","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bbi.2008.07.003","article-title":"Peripheral Cytokines Profile in Parkinson\u2019s Disease","volume":"23","author":"Reale","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_37","first-page":"192747","article-title":"Vitamin D and Alzheimer\u2019s Disease: Neurocognition to Therapeutics","volume":"2015","author":"Banerjee","year":"2015","journal-title":"Int. J. Alzheimers Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jneuroim.2010.12.007","article-title":"Reduced Thymic Output and Peripheral Na\u00efve CD4 T-Cell Alterations in Primary Progressive Multiple Sclerosis (PPMS)","volume":"233","author":"Haegert","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101422","DOI":"10.1016\/j.arr.2021.101422","article-title":"Immunosenescence and Inflammaging in the Aging Process: Age-Related Diseases or Longevity?","volume":"71","author":"Santoro","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1182\/blood-2017-06-746412","article-title":"Aging of Hematopoietic Stem Cells","volume":"131","author":"Lazare","year":"2018","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e124213","DOI":"10.1172\/jci.insight.124213","article-title":"Aged Marrow Macrophages Expand Platelet-Biased Hematopoietic Stem Cells via Interleukin-1B","volume":"4","author":"Frisch","year":"2019","journal-title":"JCI Insight"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1016\/j.celrep.2019.11.004","article-title":"Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation","volume":"29","author":"Helbling","year":"2019","journal-title":"Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/nm1578","article-title":"Telomere Dysfunction Induces Environmental Alterations Limiting Hematopoietic Stem Cell Function and Engraftment","volume":"13","author":"Ju","year":"2007","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"ra75","DOI":"10.1126\/scisignal.2000559","article-title":"MTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells","volume":"2","author":"Chen","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12979-022-00273-0","article-title":"Telomerase Deficiency Reflects Age-Associated Changes in CD4+ T Cells","volume":"19","author":"Matthe","year":"2022","journal-title":"Immun. Ageing"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e57950","DOI":"10.7554\/eLife.57950","article-title":"Autophagy in t Cells from Aged Donors Is Maintained by Spermidine and Correlates with Function and Vaccine Responses","volume":"9","author":"Alsaleh","year":"2020","journal-title":"eLife"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/ni.3003","article-title":"Chaperone-Mediated Autophagy Regulates T Cell Responses through Targeted Degradation of Negative Regulators of T Cell Activation","volume":"15","author":"Valdor","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1111\/gtc.12728","article-title":"Defective Induction of the Proteasome Associated with T-Cell Receptor Signaling Underlies T-Cell Senescence","volume":"24","author":"Arata","year":"2019","journal-title":"Genes Cells"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/j.celrep.2016.01.044","article-title":"Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence","volume":"14","author":"Spadaro","year":"2016","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1126\/science.aax0860","article-title":"T Cells with Dysfunctional Mitochondria Induce Multimorbidity and Premature Senescence","volume":"368","author":"Aranda","year":"2020","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1146\/annurev.immunol.21.120601.141110","article-title":"T Cell Anergy","volume":"21","author":"Schwartz","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.coi.2012.12.003","article-title":"T Cell Anergy, Exhaustion, Senescence, and Stemness in the Tumor Microenvironment","volume":"25","author":"Crespo","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41577-019-0180-1","article-title":"Mechanisms Underlying T Cell Ageing","volume":"19","author":"Goronzy","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41577-021-00557-4","article-title":"The Role of T Cells in Age-Related Diseases","volume":"22","author":"Carrasco","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Pieren, D.K.J., Smits, N.A.M., Imholz, S., Nagarajah, B., van Oostrom, C.T., Brandt, R.M.C., Vermeij, W.P., Doll\u00e9, M.E.T., and Guichelaar, T. (2021). Compromised DNA Repair Promotes the Accumulation of Regulatory T Cells With an Aging-Related Phenotype and Responsiveness. Front. Aging, 2.","DOI":"10.3389\/fragi.2021.667193"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1159\/000355303","article-title":"Regulatory T Cells and the Immune Aging Process: A Mini-Review","volume":"60","author":"Jagger","year":"2014","journal-title":"Gerontology"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Rocamora-Reverte, L., Melzer, F.L., W\u00fcrzner, R., and Weinberger, B. (2021). The Complex Role of Regulatory T Cells in Immunity and Aging. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.616949"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Palatella, M., Guillaume, S.M., Linterman, M.A., and Huehn, J. (2022). The Dark Side of Tregs during Aging. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.940705"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.coi.2012.04.005","article-title":"Homeostasis and Function of Regulatory T Cells in Aging","volume":"24","author":"Raynor","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1182\/blood-2010-09-307983","article-title":"B-Cell Depletion Reactivates B Lymphopoiesis in the BM and Rejuvenates the B Lineage in Aging","volume":"117","author":"Keren","year":"2011","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"De Mol, J., Kuiper, J., Tsiantoulas, D., and Foks, A.C. (2021). The Dynamics of B Cell Aging in Health and Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.733566"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12979-021-00231-2","article-title":"Analysis of the Heterogeneity of the BCR H-CDR3 Repertoire in the Bone Marrow and Spleen of 3-, 12-, and 20-Month Old Mice","volume":"18","author":"Ma","year":"2021","journal-title":"Immun. Ageing"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/acel.12055","article-title":"In Senescence, Age-Associated b Cells Secrete Tnf\u03b1 and Inhibit Survival of b-Cell Precursors","volume":"12","author":"Ratliff","year":"2013","journal-title":"Aging Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cellimm.2017.04.008","article-title":"Age-Associated B Cells (ABC) Inhibit B Lymphopoiesis and Alter Antibody Repertoires in Old Age","volume":"321","author":"Riley","year":"2017","journal-title":"Cell. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"111615","DOI":"10.1016\/j.exger.2021.111615","article-title":"Immunosenescence Evaluation of Peripheral Blood Lymphocyte Subsets in 957 Healthy Adults from 20 to 95 Years Old","volume":"157","author":"Sun","year":"2022","journal-title":"Exp. Gerontol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"eabf9277","DOI":"10.1126\/science.abf9277","article-title":"Heterogeneity of Meningeal B Cells Reveals a Lymphopoietic Niche at the CNS Borders","volume":"373","author":"Brioschi","year":"2021","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.coi.2014.04.002","article-title":"Shaping of NK Cell Subsets by Aging","volume":"29","author":"Solana","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1742-4933-3-10","article-title":"Ageing Is Associated with a Decline in Peripheral Blood CD56bright NK Cells","volume":"3","author":"Chidrawar","year":"2006","journal-title":"Immun. Ageing"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00262-015-1750-0","article-title":"Age-Related Changes in Natural Killer Cell Repertoires: Impact on NK Cell Function and Immune Surveillance","volume":"65","author":"Manser","year":"2016","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Brauning, A., Rae, M., Zhu, G., Fulton, E., Admasu, T.D., Stolzing, A., and Sharma, A. (2022). Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions. Cells, 11.","DOI":"10.3390\/cells11061017"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00262-015-1720-6","article-title":"Natural Killer Cell Immunosenescence in Acute Myeloid Leukaemia Patients: New Targets for Immunotherapeutic Strategies?","volume":"65","author":"Campos","year":"2016","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/acel.12416","article-title":"Age-Associated Changes in Long-Chain Fatty Acid Profile during Healthy Aging Promote pro-Inflammatory Monocyte Polarization via PPAR\u03b3","volume":"15","author":"Pararasa","year":"2016","journal-title":"Aging Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.arr.2013.05.006","article-title":"Phagocyte Dysfunction, Tissue Aging and Degeneration","volume":"12","author":"Li","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10522-014-9514-3","article-title":"Innate Immunesenescence: Underlying Mechanisms and Clinical Relevance","volume":"16","author":"Hazeldine","year":"2015","journal-title":"Biogerontology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.mad.2011.03.005","article-title":"Impaired in Vivo CD4+ T Cell Expansion and Differentiation in Aged Mice Is Not Solely Due to T Cell Defects: Decreased Stimulation by Aged Dendritic Cells","volume":"132","author":"Pereira","year":"2011","journal-title":"Mech. Ageing Dev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s11357-010-9191-3","article-title":"Age-Associated Impaired Plasmacytoid Dendritic Cell Functions Lead to Decreased CD4 and CD8 T Cell Immunity","volume":"33","author":"Sridharan","year":"2011","journal-title":"Age"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.4049\/jimmunol.1501006","article-title":"Loss of Phagocytic and Antigen Cross-Presenting Capacity in Aging Dendritic Cells Is Associated with Mitochondrial Dysfunction","volume":"195","author":"Chougnet","year":"2015","journal-title":"J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/s41590-020-0643-3","article-title":"Sestrins Induce Natural Killer Function in Senescent-like CD8+ T Cells","volume":"21","author":"Pereira","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e13272","DOI":"10.1111\/acel.13272","article-title":"The Role of Senescent T Cells in Immunopathology","volume":"19","author":"Covre","year":"2020","journal-title":"Aging Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e13344","DOI":"10.1111\/acel.13344","article-title":"Senescence-Associated \u03b2-Galactosidase Reveals the Abundance of Senescent CD8+ T Cells in Aging Humans","volume":"20","author":"Dewald","year":"2021","journal-title":"Aging Cell"},{"key":"ref_81","first-page":"136","article-title":"Role of Pro-Inflammatory Cytokines Released from Microglia in Alzheimer\u2019s Disease","volume":"3","author":"Wang","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"101410","DOI":"10.1016\/j.arr.2021.101410","article-title":"Targeting Immune Dysfunction in Aging","volume":"70","author":"Borgoni","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of Aging: An Expanding Universe","volume":"186","author":"Blasco","year":"2023","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0531-5565(88)90025-3","article-title":"Biomarkers of Aging","volume":"23","author":"Baker","year":"1988","journal-title":"Exp. Gerontol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"110459","DOI":"10.1016\/j.celrep.2022.110459","article-title":"Distinct Biological Ages of Organs and Systems Identified from a Multi-Omics Study","volume":"38","author":"Nie","year":"2022","journal-title":"Cell Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s Disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: Chronic Inflammation in Ageing, Cardiovascular Disease, and Frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Tan, Q., Liang, N., Zhang, X., and Li, J. (2021). Dynamic Aging: Channeled Through Microenvironment. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.702276"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1742-4933-10-12","article-title":"Immunosenescence in Vertebrates and Invertebrates","volume":"10","author":"Pawelec","year":"2013","journal-title":"Immun. Ageing"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cpt.2023.08.001","article-title":"Impact of Immunosenescence and Inflammaging on the Effects of Immune Checkpoint Inhibitors","volume":"2","author":"Hou","year":"2024","journal-title":"Cancer Pathog. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.mad.2006.11.016","article-title":"Inflammaging and Anti-Inflammaging: A Systemic Perspective on Aging and Longevity Emerged from Studies in Humans","volume":"128","author":"Franceschi","year":"2007","journal-title":"Mech. Ageing Dev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s43587-021-00049-z","article-title":"Accumulation of Cytotoxic T Cells in the Aged CNS Leads to Axon Degeneration and Contributes to Cognitive and Motor Decline","volume":"1","author":"Groh","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.jalz.2018.06.2857","article-title":"Blood-brain Barrier Breakdown, Neuroinflammation, and Cognitive Decline in Older Adults","volume":"14","author":"Bowman","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.bbi.2016.10.020","article-title":"The Effect of Systemic Inflammation on Human Brain Barrier Function","volume":"62","author":"Elwood","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.it.2009.05.001","article-title":"An Evolutionary Perspective on the Mechanisms of Immunosenescence","volume":"30","author":"Shanley","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1126\/science.1088417","article-title":"Inflammatory Blockade Restores Adult Hippocampal Neurogenesis","volume":"302","author":"Monje","year":"2003","journal-title":"Science"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Dulal, N., and Gyu, Y. (2013). Neuroinflammation on the Epigenetics of Neural Stem Cells. Neural Stem Cells\u2014New Perspectives, IntechOpen.","DOI":"10.5772\/54981"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1007\/s10571-023-01376-y","article-title":"Microglial Metabolic Reprogramming: Emerging Insights and Therapeutic Strategies in Neurodegenerative Diseases","volume":"43","author":"Miao","year":"2023","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/j.cell.2024.03.036","article-title":"From Periphery to Center Stage: 50 Years of Advancements in Innate Immunity","volume":"187","author":"Carpenter","year":"2024","journal-title":"Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41593-022-01027-3","article-title":"Gut Microbiota Drives Age-Related Oxidative Stress and Mitochondrial Damage in Microglia via the Metabolite N 6-Carboxymethyllysine","volume":"25","author":"Mossad","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/nn.4325","article-title":"Age-Related Myelin Degradation Burdens the Clearance Function of Microglia during Aging","volume":"19","author":"Safaiyan","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/s41467-018-02926-5","article-title":"A Transcriptomic Atlas of Aged Human Microglia","volume":"9","author":"Olah","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/alz.12389","article-title":"Diversity of Transcriptomic Microglial Phenotypes in Aging and Alzheimer\u2019s Disease","volume":"18","author":"Boche","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/s41593-024-01620-8","article-title":"Identification of Senescent, TREM2-Expressing Microglia in Aging and Alzheimer\u2019s Disease Model Mouse Brain","volume":"27","author":"Rachmian","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e13094","DOI":"10.1111\/acel.13094","article-title":"Tissue Specificity of Senescent Cell Accumulation during Physiologic and Accelerated Aging of Mice","volume":"19","author":"Yousefzadeh","year":"2020","journal-title":"Aging Cell"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41556-023-01158-0","article-title":"Autophagy Enables Microglia to Engage Amyloid Plaques and Prevents Microglial Senescence","volume":"25","author":"Choi","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s00401-024-02727-9","article-title":"Characterisation of Premature Cell Senescence in Alzheimer\u2019s Disease Using Single Nuclear Transcriptomics","volume":"147","author":"Fancy","year":"2024","journal-title":"Acta Neuropathol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nn.4030","article-title":"Host Microbiota Constantly Control Maturation and Function of Microglia in the CNS","volume":"18","author":"Erny","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1084\/jem.20182386","article-title":"Sex-Specific Effects of Microbiome Perturbations on Cerebral Ab Amyloidosis and Microglia Phenotypes","volume":"216","author":"Dodiya","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/s42003-023-05027-2","article-title":"Cellular Senescence in White Matter Microglia Is Induced during Ageing in Mice and Exacerbates the Neuroinflammatory Phenotype","volume":"6","author":"Matsudaira","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.chom.2017.03.002","article-title":"Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction","volume":"21","author":"Thevaranjan","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e13450","DOI":"10.1111\/acel.13450","article-title":"Identification of Distinct and Age-Dependent P16High Microglia Subtypes","volume":"20","author":"Talma","year":"2021","journal-title":"Aging Cell"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1038\/s41593-020-0682-y","article-title":"Author Correction: Lipid-Droplet-Accumulating Microglia Represent a Dysfunctional and Proinflammatory State in the Aging Brain","volume":"23","author":"Marschallinger","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s00401-020-02129-7","article-title":"Niacin-Mediated Rejuvenation of Macrophage\/Microglia Enhances Remyelination of the Aging Central Nervous System","volume":"139","author":"Rawji","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41586-019-1088-4","article-title":"CD22 Blockade Restores Homeostatic Microglial Phagocytosis in Ageing Brains","volume":"568","author":"Pluvinage","year":"2019","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1016\/j.cell.2021.08.002","article-title":"Rescue of a Lysosomal Storage Disorder Caused by Grn Loss of Function with a Brain Penetrant Progranulin Biologic","volume":"184","author":"Logan","year":"2021","journal-title":"Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s12974-023-02855-1","article-title":"ATP-P2X7R-Mediated Microglia Senescence Aggravates Retinal Ganglion Cell Injury in Chronic Ocular Hypertension","volume":"20","author":"Wei","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12974-017-0840-7","article-title":"Proteomic Anaysis of Aged Microglia: Shifts in Transcription, Bioenergetics, and Nutrient Response","volume":"14","author":"Flowers","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1002\/ana.26770","article-title":"Ferroptosis of Microglia in Aging Human White Matter Injury","volume":"94","author":"Adeniyi","year":"2023","journal-title":"Ann. Neurol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"109228","DOI":"10.1016\/j.celrep.2021.109228","article-title":"Replicative Senescence Dictates the Emergence of Disease-Associated Microglia and Contributes to A\u03b2 Pathology","volume":"35","author":"Hu","year":"2021","journal-title":"Cell Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40035-024-00402-3","article-title":"Emerging Role of Senescent Microglia in Brain Aging-Related Neurodegenerative Diseases","volume":"13","author":"Rim","year":"2024","journal-title":"Transl. Neurodegener."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41586-023-06783-1","article-title":"CHIT1-Positive Microglia Drive Motor Neuron Ageing in the Primate Spinal Cord","volume":"624","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.stem.2024.03.013","article-title":"Osteopontin Drives Neuroinflammation and Cell Loss in MAPT-N279K Frontotemporal Dementia Patient Neurons","volume":"31","author":"Lam","year":"2024","journal-title":"Cell Stem Cell"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/s43587-022-00257-1","article-title":"A Distinct Astrocyte Subtype in the Aging Mouse Brain Characterized by Impaired Protein Homeostasis","volume":"2","author":"Lee","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/glia.24147","article-title":"Astrocyte Immunosenescence and Deficits in Interleukin 10 Signaling in the Aged Brain Disrupt the Regulation of Microglia Following Innate Immune Activation","volume":"70","author":"Hans","year":"2022","journal-title":"Glia"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e13521","DOI":"10.1111\/acel.13521","article-title":"Loss of Lamin-B1 and Defective Nuclear Morphology Are Hallmarks of Astrocyte Senescence in Vitro and in the Aging Human Hippocampus","volume":"21","author":"Matias","year":"2022","journal-title":"Aging Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1016\/j.yexcr.2010.06.021","article-title":"Stress-Induced Senescence in Human and Rodent Astrocytes","volume":"316","author":"Bitto","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Limbad, C., Oron, T.R., Alimirah, F., Davalos, A.R., Tracy, T.E., Gan, L., Desprez, P.Y., and Campisi, J. (2020). Astrocyte Senescence Promotes Glutamate Toxicity in Cortical Neurons. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0227887"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"109419","DOI":"10.1016\/j.celrep.2021.109419","article-title":"Tau Oligomer Induced HMGB1 Release Contributes to Cellular Senescence and Neuropathology Linked to Alzheimer\u2019s Disease and Frontotemporal Dementia","volume":"36","author":"Gaikwad","year":"2021","journal-title":"Cell Rep."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Shang, D., Hong, Y., Xie, W., Tu, Z., and Xu, J. (2020). Interleukin-1\u03b2 Drives Cellular Senescence of Rat Astrocytes Induced by Oligomerized Amyloid \u03b2 Peptide and Oxidative Stress. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00929"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e13465","DOI":"10.1111\/acel.13465","article-title":"YAP Prevents Premature Senescence of Astrocytes and Cognitive Decline of Alzheimer\u2019s Disease through Regulating CDK6 Signaling","volume":"20","author":"Xu","year":"2021","journal-title":"Aging Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Archie, S.R., Al Shoyaib, A., and Cucullo, L. (2021). Blood-Brain Barrier Dysfunction in Cns Disorders and Putative Therapeutic Targets: An Overview. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111779"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1038\/s41593-017-0010-3","article-title":"Social Stress Induces Neurovascular Pathology Promoting Depression","volume":"20","author":"Menard","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1177\/0271678X20951995","article-title":"Regulation of Blood\u2013Brain Barrier Integrity by Microglia in Health and Disease: A Therapeutic Opportunity","volume":"40","author":"Ronaldson","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.2174\/138161212802002625","article-title":"Blood-Brain Barrier Integrity and Glial Support: Mechanisms That Can Be Targeted for Novel Therapeutic Approaches in Stroke","volume":"18","author":"Ronaldson","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1124\/pr.57.2.4","article-title":"The Blood-Brain Barrier\/Neurovascular Unit in Health and Disease","volume":"57","author":"Hawkins","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1042\/BST20220830","article-title":"The Role of the Blood-Brain Barrier during Neurological Disease and Infection","volume":"51","author":"Patabendige","year":"2023","journal-title":"Biochem. Soc. Trans."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S0165-0173(01)00102-3","article-title":"Molecular and Cellular Permeability Control at the Blood-Brain Barrier","volume":"36","author":"Gloor","year":"2001","journal-title":"Brain Res. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood-Brain Barrier Breakdown in the Aging Human Hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood\u2013Brain Barrier Breakdown Is an Early Biomarker of Human Cognitive Dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and Function of the Blood-Brain Barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1124\/pr.117.014647","article-title":"Neuroimmune Axes of the Blood-Brain Barriers and Blood-Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions","volume":"70","author":"Erickson","year":"2018","journal-title":"Pharmacol. Rev."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e4510","DOI":"10.1002\/nbm.4510","article-title":"Alzheimer\u2019s Disease Pathology Is Associated with Earlier Alterations to Blood\u2013Brain Barrier Water Permeability Compared with Healthy Ageing in TgF344-AD Rats","volume":"34","author":"Dickie","year":"2021","journal-title":"NMR Biomed."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12987-020-00230-3","article-title":"A Blood\u2013Brain Barrier Overview on Structure, Function, Impairment, and Biomarkers of Integrity","volume":"17","author":"Kadry","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1111\/apha.12250","article-title":"The Neurovascular Unit\u2014Concept Review","volume":"210","author":"Muoio","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10571-016-0334-7","article-title":"The Science of Vascular Contributions to Cognitive Impairment and Dementia (VCID): A Framework for Advancing Research Priorities in the Cerebrovascular Biology of Cognitive Decline","volume":"36","author":"Corriveau","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/nan.12552","article-title":"A Cortical Microvascular Structure in Vascular Dementia, Alzheimer\u2019s Disease, Frontotemporal Lobar Degeneration and Nondemented Controls: A Sign of Angiogenesis Due to Brain Ischaemia?","volume":"45","author":"Englund","year":"2019","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Parodi-Rull\u00e1n, R.M., Javadov, S., and Fossati, S. (2021). Dissecting the Crosstalk between Endothelial Mitochondrial Damage, Vascular Inflammation, and Neurodegeneration in Cerebral Amyloid Angiopathy and Alzheimer\u2019s Disease. Cells, 10.","DOI":"10.3390\/cells10112903"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/jcmm.13980","article-title":"Age-Related Ultrastructural Changes of the Basement Membrane in the Mouse Blood-Brain Barrier","volume":"23","author":"Ceafalan","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1111\/bpa.12888","article-title":"Loss of Capillary Pericytes and the Blood\u2013Brain Barrier in White Matter in Poststroke and Vascular Dementias and Alzheimer\u2019s Disease","volume":"30","author":"Ding","year":"2020","journal-title":"Brain Pathol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.neuint.2010.07.002","article-title":"Expression and Regulation of Toll-like Receptors in Cerebral Endothelial Cells","volume":"57","author":"Nagyoszi","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s11481-015-9591-3","article-title":"Activation of Cannabinoid Type Two Receptors (CB2) Diminish Inflammatory Responses in Macrophages and Brain Endothelium","volume":"10","author":"Persidsky","year":"2015","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Konsman, J.P. (2022). Cytokines in the Brain and Neuroinflammation: We Didn\u2019t Starve the Fire!. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020140"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neurobiolaging.2017.05.011","article-title":"Aging Alters MRNA Expression of Amyloid Transporter Genes at the Blood-Brain Barrier","volume":"57","author":"Osgood","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Lakhan, S.E., Kirchgessner, A., Tepper, D., and Leonard, A. (2013). Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke. Front. Neurol., 4.","DOI":"10.3389\/fneur.2013.00032"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"E1256","DOI":"10.1212\/WNL.0000000000007094","article-title":"Systemic Inflammation during Midlife and Cognitive Change over 20 Years: The ARIC Study","volume":"92","author":"Walker","year":"2019","journal-title":"Neurology"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bbi.2015.03.015","article-title":"Brain Morphology Links Systemic Inflammation to Cognitive Function in Midlife Adults","volume":"48","author":"Marsland","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1212\/WNL.0b013e3181b6bb95","article-title":"Systemic Inflammation and Disease Progression in Alzheimer Disease","volume":"73","author":"Holmes","year":"2009","journal-title":"Neurology"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Lier, J., Streit, W.J., and Bechmann, I. (2021). Beyond Activation: Characterizing Microglial Functional Phenotypes. Cells, 10.","DOI":"10.3390\/cells10092236"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1038\/s41593-022-01183-6","article-title":"CD8+ T Cells Induce Interferon-Responsive Oligodendrocytes and Microglia in White Matter Aging","volume":"25","author":"Kaya","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/2046-2395-1-8","article-title":"Immunosenescence, Inflammation and Alzheimer\u2019s Disease","volume":"1","author":"Martorana","year":"2012","journal-title":"Longev. Heal."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.pneurobio.2017.07.006","article-title":"Impact of Aging Immune System on Neurodegeneration and Potential Immunotherapies","volume":"157","author":"Liang","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/j.1600-0404.2007.00894.x","article-title":"Circulating Interleukin-15 and RANTES Chemokine in Parkinson\u2019s Disease","volume":"116","author":"Rentzos","year":"2007","journal-title":"Acta Neurol. Scand."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.brainres.2014.09.008","article-title":"The Role of the Immune System in Neurodegenerative Disorders: Adaptive or Maladaptive?","volume":"1617","author":"Doty","year":"2015","journal-title":"Brain Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2020.12.040","article-title":"Functional Characterization of the Dural Sinuses as a Neuroimmune Interface","volume":"184","author":"Rustenhoven","year":"2021","journal-title":"Cell"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41586-019-1362-5","article-title":"Single-Cell Analysis Reveals T Cell Infiltration in Old Neurogenic Niches","volume":"571","author":"Dulken","year":"2019","journal-title":"Nature"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1212\/WNL.0b013e3182a2ce0e","article-title":"T-Cell Homeostasis in Pediatric Multiple Sclerosis Old Cells in Young Patients","volume":"81","author":"Balint","year":"2013","journal-title":"Neurology"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/s41593-025-01955-w","article-title":"Microglia Activation Orchestrates CXCL10-Mediated CD8+ T Cell Recruitment to Promote Aging-Related White Matter Degeneration","volume":"28","author":"Groh","year":"2025","journal-title":"Nat. Neurosci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1159\/000358437","article-title":"Premature Immunosenescence Is Associated with Memory Dysfunction in Rheumatoid Arthritis","volume":"22","author":"Petersen","year":"2014","journal-title":"Neuroimmunomodulation"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1038\/s41467-019-11638-3","article-title":"Oligodendrocyte Precursor Cells Present Antigen and Are Cytotoxic Targets in Inflammatory Demyelination","volume":"10","author":"Kirby","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.cell.2018.07.049","article-title":"Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping","volume":"175","author":"Pantelyushin","year":"2018","journal-title":"Cell"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.parkreldis.2005.07.005","article-title":"Alterations of T-Lymphocyte Populations in Parkinson Disease","volume":"11","author":"Baba","year":"2005","journal-title":"Park. Relat. Disord."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Mayne, K., White, J.A., McMurran, C.E., Rivera, F.J., and de la Fuente, A.G. (2020). Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.572090"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1146\/annurev-cellbio-011620-034148","article-title":"B Cell Immunosenescence","volume":"36","author":"Frasca","year":"2020","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"E1316","DOI":"10.1073\/pnas.1525466113","article-title":"The Adaptive Immune System Restrains Alzheimer\u2019s Disease Pathogenesis by Modulating Microglial Function","volume":"113","author":"Marsh","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"6039171","DOI":"10.1155\/2018\/6039171","article-title":"The Role of Immunosenescence in Neurodegenerative Diseases","volume":"2018","author":"Costantini","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.neubiorev.2017.01.044","article-title":"Contribution of Neuroinflammation and Immunity to Brain Aging and the Mitigating Effects of Physical and Cognitive Interventions","volume":"75","author":"Wenger","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_179","first-page":"1726","article-title":"Neuroinflammaging: A Tight Line Between Normal Aging and Age-Related Neurodegenerative Disorders","volume":"15","author":"Soraci","year":"2024","journal-title":"Aging Dis."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuropharm.2014.10.028","article-title":"Microglial Priming and Enhanced Reactivity to Secondary Insult in Aging, and Traumatic CNS Injury, and Neurodegenerative Disease","volume":"96","author":"Norden","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Teissier, T., Boulanger, E., and Cox, L.S. (2022). Interconnections between Inflammageing and Immunosenescence during Ageing. Cells, 11.","DOI":"10.3390\/cells11030359"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Schuettpelz, L.G., and Link, D.C. (2013). Regulation of Hematopoietic Stem Cell Activity by Inflammation. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00204"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Boahen, A., Hu, D., Adams, M.J., Nicholls, P.K., Greene, W.K., and Ma, B. (2023). Bidirectional Crosstalk between the Peripheral Nervous System and Lymphoid Tissues\/Organs. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1254054"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.it.2024.08.006","article-title":"The Putative Contribution of Cellular Senescence to Driving Tauopathies","volume":"45","author":"Karabag","year":"2024","journal-title":"Trends Immunol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1038\/s41467-025-57632-w","article-title":"Senescent-like Microglia Limit Remyelination through the Senescence Associated Secretory Phenotype","volume":"16","author":"Gross","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1016\/j.neuron.2024.09.006","article-title":"Alzheimer\u2019s Disease-Linked Risk Alleles Elevate Microglial CGAS-Associated Senescence and Neurodegeneration in a Tauopathy Model","volume":"112","author":"Carling","year":"2024","journal-title":"Neuron"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12974-023-03003-5","article-title":"Peripheral Blood Amyloid-\u03b2 Involved in the Pathogenesis of Alzheimer\u2019s Disease via Impacting on Peripheral Innate Immune Cells","volume":"21","author":"Shi","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1038\/s41467-024-45627-y","article-title":"Amyloid-\u03b2 Aggregates Activate Peripheral Monocytes in Mild Cognitive Impairment","volume":"15","author":"Parbo","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4049\/jimmunol.1801506","article-title":"Widespread Tau-Specific CD4 T Cell Reactivity in the General Population","volume":"203","author":"Pham","year":"2019","journal-title":"J. Immunol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nature22815","article-title":"T Cells from Patients with Parkinson\u2019s Disease Recognize \u03b1-Synuclein Peptides","volume":"546","author":"Sulzer","year":"2017","journal-title":"Nature"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/glia.20468","article-title":"Microglia Derived from Aging Mice Exhibit an Altered Inflammatory Profile","volume":"55","author":"Sierra","year":"2007","journal-title":"Glia"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1089\/ars.2014.6022","article-title":"Methionine Sulfoxide Reductase A Negatively Controls Microglia-Mediated Neuroinflammation via Inhibiting ROS\/MAPKs\/NF-\u039aB Signaling Pathways Through a Catalytic Antioxidant Function","volume":"22","author":"Fan","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nn.4475","article-title":"The Role of Peripheral Immune Cells in the CNS in Steady State and Disease","volume":"20","author":"Prinz","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"11368","DOI":"10.1038\/s41598-025-96456-y","article-title":"Microglial TLR4-Lyn Kinase Is a Critical Regulator of Neuroinflammation, A\u03b2 Phagocytosis, Neuronal Damage, and Cell Survival in Alzheimer\u2019s Disease","volume":"15","author":"Islam","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12979-023-00396-y","article-title":"Aging Gene Signature of Memory CD8+ T Cells Is Associated with Neurocognitive Functioning in Alzheimer\u2019s Disease","volume":"20","author":"Young","year":"2023","journal-title":"Immun. Ageing"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41586-019-1895-7","article-title":"Clonally Expanded CD8 T Cells Patrol the Cerebrospinal Fluid in Alzheimer\u2019s Disease","volume":"577","author":"Gate","year":"2020","journal-title":"Nature"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0197-4580(02)00043-X","article-title":"Telomere Shortening in T Cells Correlates with Alzheimer\u2019s Disease Status","volume":"24","author":"Panossian","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"5368","DOI":"10.1007\/s00415-022-11190-z","article-title":"Changes of T Lymphocyte Subpopulations and Their Roles in Predicting the Risk of Parkinson\u2019s Disease","volume":"269","author":"He","year":"2022","journal-title":"J. Neurol."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Huang, Y., Liu, H., Hu, J., Han, C., Zhong, Z., Luo, W., Zhang, Y., and Ling, F. (2021). Significant Difference of Immune Cell Fractions and Their Correlations With Differential Expression Genes in Parkinson\u2019s Disease. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.686066"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1186\/s12967-021-03055-2","article-title":"Increased Tc17 Cell Levels and Imbalance of Na\u00efve\/Effector Immune Response in Parkinson\u2019s Disease Patients in a Two-Year Follow-up: A Case Control Study","volume":"19","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"105890","DOI":"10.1016\/j.parkreldis.2023.105890","article-title":"Abnormal Immune Function of B Lymphocyte in Peripheral Blood of Parkinson\u2019s Disease","volume":"116","author":"Zhang","year":"2023","journal-title":"Park. Relat. Disord."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/ana.26034","article-title":"Lower Lymphocyte Count Is Associated With Increased Risk of Parkinson\u2019s Disease","volume":"89","author":"Jensen","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/ana.25614","article-title":"Peripheral Immune Biomarkers and Neurodegenerative Diseases: A Prospective Cohort Study with 20 Years of Follow-Up","volume":"86","author":"Yazdani","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1002\/mds.29369","article-title":"Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson\u2019s Disease","volume":"38","year":"2023","journal-title":"Mov. Disord."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1136\/jnnp-2022-330394","article-title":"Prognostic Significance of Peripheral Neutrophils and Lymphocytes in Early Untreated Parkinson\u2019s Disease: An 8-Year Follow-up Study","volume":"94","author":"Kim","year":"2023","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12974-018-1206-5","article-title":"Abnormalities of Age-Related T Cell Senescence in Parkinson\u2019s Disease","volume":"15","author":"Wijeyekoon","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s12974-021-02287-9","article-title":"T Lymphocyte Senescence Is Attenuated in Parkinson\u2019s Disease","volume":"18","author":"Kouli","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41420-024-01816-8","article-title":"Glial Senescence Enhances \u03b1-Synuclein Pathology Owing to Its Insufficient Clearance Caused by Autophagy Dysfunction","volume":"10","author":"Hong","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00401-015-1504-2","article-title":"Age-Dependent Defects of Alpha-Synuclein Oligomer Uptake in Microglia and Monocytes","volume":"131","author":"Bliederhaeuser","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"103919","DOI":"10.1016\/j.mcn.2024.103919","article-title":"Alpha-Synuclein Pathology Is Associated with Astrocyte Senescence in a Midbrain Organoid Model of Familial Parkinson\u2019s Disease","volume":"128","author":"Muwanigwa","year":"2024","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1038\/s41418-023-01216-y","article-title":"The CGAS-STING-YY1 Axis Accelerates Progression of Neurodegeneration in a Mouse Model of Parkinson\u2019s Disease via LCN2-Dependent Astrocyte Senescence","volume":"30","author":"Jiang","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_212","first-page":"182","article-title":"Infiltration of CD4+ Lymphocytes into the Brain Contributes to Neurodegeneration in a Mouse Model of Parkinson Disease","volume":"119","author":"Brochard","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1212\/WNL.46.3.791","article-title":"Decrease of the D3 Dopamine Receptor MRNA Expression in Lymphocytes from Patients with Parkinson\u2019s Disease","volume":"46","author":"Nagai","year":"1996","journal-title":"Neurology"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1212\/WNL.58.12.1809","article-title":"Oxidative Damage and Cytogenetic Analysis in Leukocytes of Parkinson\u2019s Disease Patients","volume":"58","author":"Migliore","year":"2002","journal-title":"Neurology"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"R105","DOI":"10.1093\/hmg\/ddx247","article-title":"Ageing as a Risk Factor for ALS\/FTD","volume":"26","author":"Niccoli","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"fcaa124","DOI":"10.1093\/braincomms\/fcaa124","article-title":"Immunity in Amyotrophic Lateral Sclerosis: Blurred Lines between Excessive Inflammation and Inefficient Immune Responses","volume":"2","author":"Markovinovic","year":"2020","journal-title":"Brain Commun."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13024-018-0292-2","article-title":"Tissue-Enhanced Plasma Proteomic Analysis for Disease Stratification in Amyotrophic Lateral Sclerosis","volume":"13","author":"Zubiri","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"e200042","DOI":"10.1212\/NXI.0000000000200042","article-title":"Senescent-like Blood Lymphocytes and Disease Progression in Amyotrophic Lateral Sclerosis","volume":"10","author":"Yildiz","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12974-023-03007-1","article-title":"CD4 T-Cell Aging Exacerbates Neuroinflammation in a Late-Onset Mouse Model of Amyotrophic Lateral Sclerosis","volume":"21","author":"Zaccai","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_220","doi-asserted-by":"crossref","unstructured":"Trias, E., Beilby, P.R., Kovacs, M., Ibarburu, S., Varela, V., Barreto-N\u00fa\u00f1ez, R., Bradford, S.C., Beckman, J.S., and Barbeito, L. (2019). Emergence of Microglia Bearing Senescence Markers during Paralysis Progression in a Rat Model of Inherited ALS. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2019.00042"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/nan.12559","article-title":"Expression of P16 and P21 in the Frontal Association Cortex of ALS\/MND Brains Suggests Neuronal Cell Cycle Dysregulation and Astrocyte Senescence in Early Stages of the Disease","volume":"46","author":"Garwood","year":"2020","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1093\/brain\/awr074","article-title":"Endogenous Regulatory T Lymphocytes Ameliorate Amyotrophic Lateral Sclerosis in Mice and Correlate with Disease Progression in Patients with Amyotrophic Lateral Sclerosis","volume":"134","author":"Beers","year":"2011","journal-title":"Brain"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.expneurol.2012.06.011","article-title":"Transformation from a Neuroprotective to a Neurotoxic Microglial Phenotype in a Mouse Model of ALS","volume":"237","author":"Liao","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13024-020-00397-1","article-title":"The Role of TDP-43 Mislocalization in Amyotrophic Lateral Sclerosis","volume":"15","author":"Suk","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"eadg7162","DOI":"10.1126\/scitranslmed.adg7162","article-title":"Mis-Spliced Transcripts Generate de Novo Proteins in TDP-43\u2013Related Als\/FTD","volume":"16","author":"Seddighi","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_226","unstructured":"Chizari, S., Zanovello, M., Kong, S., Saigal, V., Brown, A.-L., Turchetti, V., Zampedri, L., Skorupinska, I., Minicuci, G.M., and Paron, F. (2025). TDP-43 Pathology Induces CD8+ T Cell Activation through Cryptic Epitope Recognition. bioRxiv."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"e89530","DOI":"10.1172\/jci.insight.89530","article-title":"ALS Patients\u2019 Regulatory T Lymphocytes Are Dysfunctional, and Correlate with Disease Progression Rate and Severity","volume":"2","author":"Beers","year":"2017","journal-title":"JCI Insight"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1016\/j.neuron.2021.05.020","article-title":"C9orf72 Deficiency Promotes Microglial-Mediated Synaptic Loss in Aging and Amyloid Accumulation","volume":"109","author":"Lall","year":"2021","journal-title":"Neuron"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"4576","DOI":"10.4049\/jimmunol.1502448","article-title":"Age-Associated B Cells with Proinflammatory Characteristics Are Expanded in a Proportion of Multiple Sclerosis Patients","volume":"197","author":"Claes","year":"2016","journal-title":"J. Immunol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jneuroim.2010.02.005","article-title":"Thymic Involution and Proliferative T-Cell Responses in Multiple Sclerosis","volume":"221","author":"Duszczyszyn","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jneuroim.2006.09.008","article-title":"Increase of CD8+ T-Effector Memory Cells in Peripheral Blood of Patients with Relapsing-Remitting Multiple Sclerosis Compared to Healthy Controls","volume":"183","author":"Haegele","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"2284247","DOI":"10.1080\/19490976.2023.2284247","article-title":"Efficacy of Fecal Microbiota Transplantation in Patients with Parkinson\u2019s Disease: Clinical Trial Results from a Randomized, Placebo-Controlled Design","volume":"15","author":"Cheng","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S1474-4422(22)00184-3","article-title":"Ageing and Multiple Sclerosis","volume":"22","author":"Graves","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"e13630","DOI":"10.1111\/acel.13630","article-title":"Accumulation of PTreg Cells Is Detrimental in Late-Onset (Aged) Mouse Model of Multiple Sclerosis","volume":"21","author":"Wang","year":"2022","journal-title":"Aging Cell"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.1093\/brain\/awv289","article-title":"Retinoid X Receptor Activation Reverses Age-Related Deficiencies in Myelin Debris Phagocytosis and Remyelination","volume":"138","author":"Natrajan","year":"2015","journal-title":"Brain"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"e158153","DOI":"10.1172\/jci.insight.158153","article-title":"Biological Aging of CNS-Resident Cells Alters the Clinical Course and Immunopathology of Autoimmune Demyelinating Disease","volume":"7","author":"Atkinson","year":"2022","journal-title":"JCI Insight"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"e14491","DOI":"10.1111\/acel.14491","article-title":"Disease Aggravation With Age in an Experimental Model of Multiple Sclerosis: Role of Immunosenescence","volume":"24","author":"Dema","year":"2025","journal-title":"Aging Cell"},{"key":"ref_238","doi-asserted-by":"crossref","unstructured":"Thakolwiboon, S., Mills, E.A., Yang, J., Doty, J., Belkin, M.I., Cho, T., Schultz, C., and Mao-Draayer, Y. (2023). Immunosenescence and Multiple Sclerosis: Inflammaging for Prognosis and Therapeutic Consideration. Front. Aging, 4.","DOI":"10.3389\/fragi.2023.1234572"},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Lassmann, H. (2019). Pathogenic Mechanisms Associated with Different Clinical Courses of Multiple Sclerosis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2018.03116"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12974-025-03425-3","article-title":"Senescent Cell Reduction Does Not Improve Recovery in Mice under Experimental Autoimmune Encephalomyelitis (EAE) Induced Demyelination","volume":"22","author":"Manavi","year":"2025","journal-title":"J. Neuroinflamm."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"128","DOI":"10.14283\/jpad.2020.4","article-title":"Cortical \u03b2-Amyloid in Older Adults Is Associated with Multidomain Interventions with and without Omega 3 Polyunsaturated Fatty Acid Supplementation","volume":"7","author":"Hooper","year":"2020","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41577-022-00684-6","article-title":"Inflammation and Immune Dysfunction in Parkinson Disease","volume":"22","author":"Tansey","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","article-title":"Inflammation and Aging: Signaling Pathways and Intervention Therapies","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nm.4010","article-title":"Clearance of Senescent Cells by ABT263 Rejuvenates Aged Hematopoietic Stem Cells in Mice","volume":"22","author":"Chang","year":"2016","journal-title":"Nat. Med."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41586-018-0543-y","article-title":"Clearance of Senescent Glial Cells Prevents Tau-Dependent Pathology and Cognitive Decline","volume":"562","author":"Bussian","year":"2018","journal-title":"Nature"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/978-981-13-3681-2_17","article-title":"Neurovascular Ageing and Age-Related Diseases","volume":"91","author":"Kalaria","year":"2019","journal-title":"Subcell. Biochem."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1038\/s41591-023-02543-w","article-title":"Senolytic Therapy in Mild Alzheimer\u2019s Disease: A Phase 1 Feasibility Trial","volume":"29","author":"Gonzales","year":"2023","journal-title":"Nat. Med."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.ebiom.2018.12.052","article-title":"Senolytics in Idiopathic Pulmonary Fibrosis: Results from a First-in-Human, Open-Label, Pilot Study","volume":"40","author":"Justice","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/joim.13141","article-title":"Senolytic Drugs: From Discovery to Translation","volume":"288","author":"Kirkland","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"20851","DOI":"10.18632\/oncotarget.4930","article-title":"Splenocytes Derived from Young WT Mice Prevent AD Progression in APPswe\/PSENldE9 Transgenic Mice","volume":"6","author":"Wang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41586-022-05388-4","article-title":"Blocking PD-L1\u2013PD-1 Improves Senescence Surveillance and Ageing Phenotypes","volume":"611","author":"Wang","year":"2022","journal-title":"Nature"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/s41556-024-01465-0","article-title":"P16-Dependent Increase of PD-L1 Stability Regulates Immunosurveillance of Senescent Cells","volume":"26","author":"Majewska","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"110243","DOI":"10.1016\/j.isci.2024.110243","article-title":"Neuronal-Enriched Small Extracellular Vesicles Trigger a PD-L1-Mediated Broad Suppression of T Cells in Parkinson\u2019s Disease","volume":"27","author":"Chen","year":"2024","journal-title":"iScience"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.arr.2017.01.001","article-title":"Gut Microbiota: A Player in Aging and a Target for Anti-Aging Intervention","volume":"35","author":"Vaiserman","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Ristori, S., Bertoni, G., Bientinesi, E., and Monti, D. (2025). The Role of Nutraceuticals and Functional Foods in Mitigating Cellular Senescence and Its Related Aspects: A Key Strategy for Delaying or Preventing Aging and Neurodegenerative Disorders. Nutrients, 17.","DOI":"10.20944\/preprints202504.0821.v1"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3233\/JAD-2011-101803","article-title":"Understanding the Broad-Spectrum Neuroprotective Action Profile of Green Tea Polyphenols in Aging and Neurodegenerative Diseases","volume":"25","author":"Mandel","year":"2011","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.freeradbiomed.2004.01.001","article-title":"Flavonoids: Antioxidants or Signalling Molecules?","volume":"36","author":"Williams","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/cmi.2017.153","article-title":"CD8+CD28- T Cells: Not Only Age-Related Cells but a Subset of Regulatory T Cells","volume":"15","author":"Chen","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"13278","DOI":"10.1038\/s41598-023-39279-z","article-title":"The Effect of Resveratrol, Curcumin and Quercetin Combination on Immuno-Suppression of Tumor Microenvironment for Breast Tumor-Bearing Mice","volume":"13","author":"Li","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"108634","DOI":"10.1016\/j.jnutbio.2021.108634","article-title":"Dietary Polyphenols Suppress Chronic Inflammation by Modulation of Multiple Inflammation-Associated Cell Signaling Pathways","volume":"93","author":"Jantan","year":"2021","journal-title":"J. Nutr. Biochem."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1084\/jem.20161066","article-title":"Metabolic Reprogramming of Human CD8+ Memory T Cells through Loss of SIRT1","volume":"215","author":"Jeng","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1038\/s41419-020-03238-7","article-title":"Telomeric Injury by KML001 in Human T Cells Induces Mitochondrial Dysfunction through the P53-PGC-1\u03b1 Pathway","volume":"11","author":"Schank","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/biof.1396","article-title":"Resveratrol, Pterostilbene, and Dementia","volume":"44","author":"Lange","year":"2018","journal-title":"BioFactors"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/S0891-5849(00)00195-7","article-title":"Bioavailability and Metabolism of the Flavonol Quercetin in the Pig","volume":"28","author":"Ader","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1089\/jmf.2017.4078","article-title":"Beneficial Effects of Flavonoids Against Parkinson\u2019s Disease","volume":"21","author":"Jung","year":"2018","journal-title":"J. Med. Food"},{"key":"ref_266","doi-asserted-by":"crossref","unstructured":"Zheng, Q., Kebede, M.T., Kemeh, M.M., Islam, S., Lee, B., Bleck, S.D., Wurfl, L.A., and Lazo, N.D. (2019). Inhibition of the Self-Assembly of A\u03b2 and of Tau by Polyphenols: Mechanistic Studies. Molecules, 24.","DOI":"10.3390\/molecules24122316"},{"key":"ref_267","doi-asserted-by":"crossref","unstructured":"Ferreira, C., Vieira, P., S\u00e1, H., Malva, J., Castelo-Branco, M., Reis, F., and Viana, S. (2024). Polyphenols: Immunonutrients Tipping the Balance of Immunometabolism in Chronic Diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1360065"},{"key":"ref_268","doi-asserted-by":"crossref","unstructured":"Shakoor, H., Feehan, J., Apostolopoulos, V., Platat, C., Al Dhaheri, A.S., Ali, H.I., Ismail, L.C., Bosevski, M., and Stojanovska, L. (2021). Immunomodulatory Effects of Dietary Polyphenols. Nutrients, 13.","DOI":"10.3390\/nu13030728"},{"key":"ref_269","doi-asserted-by":"crossref","unstructured":"Perlmutter, A., Bland, J.S., Chandra, A., Malani, S.S., Smith, R., Mendez, T.L., and Dwaraka, V.B. (2024). The Impact of a Polyphenol-Rich Supplement on Epigenetic and Cellular Markers of Immune Age: A Pilot Clinical Study. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1474597"},{"key":"ref_270","doi-asserted-by":"crossref","unstructured":"Azzolino, D., Bertoni, C., De Cosmi, V., Spolidoro, G.C.I., Agostoni, C., Lucchi, T., and Mazzocchi, A. (2024). Omega-3 Polyunsatured Fatty Acids and Physical Performance across the Lifespan: A Narrative Review. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1414132"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1093\/ajcn\/84.6.1277","article-title":"Polyunsaturated Fatty Acids, Membrane Organization, T Cells, and Antigen Presentation","volume":"84","author":"Shaikh","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"9173","DOI":"10.1523\/JNEUROSCI.1000-15.2015","article-title":"Omega-3 Fatty Acids Augment the Actions of Nuclear Receptor Agonists in a Mouse Model of Alzheimer\u2019s Disease","volume":"35","author":"Casali","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.neuron.2004.08.013","article-title":"Docosahexaenoic Acid Protects from Dendritic Pathology in an Alzheimer\u2019s Disease Mouse Model","volume":"43","author":"Calon","year":"2004","journal-title":"Neuron"},{"key":"ref_274","doi-asserted-by":"crossref","unstructured":"Arsenault, D., Julien, C., Tremblay, C., and Calon, F. (2011). DHA Improves Cognition and Prevents Dysfunction of Entorhinal Cortex Neurons in 3xTg-AD Mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017397"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/jnr.22266","article-title":"DHA Diet Reduces AD Pathology in Young APPswe\/PS1\u0394E9 Transgenic Mice: Possible Gender Effects","volume":"88","author":"Perez","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/j.1460-9568.2005.04253.x","article-title":"Dietary N-3 Polyunsaturated Fatty Acid Depletion Activates Caspases and Decreases NMDA Receptors in the Brain of a Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"22","author":"Calon","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_277","doi-asserted-by":"crossref","unstructured":"Morgese, M.G., Schiavone, S., Bove, M., Colia, A.L., Dimonte, S., Tucci, P., and Trabace, L. (2021). N-3 PUFA Prevent Oxidative Stress in a Rat Model of Beta-Amyloid-Induced Toxicity. Pharmaceuticals, 14.","DOI":"10.3390\/ph14040339"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.tifs.2017.09.003","article-title":"Omega-3 Polyunsaturated Fatty Acids and Brain Health: Preclinical Evidence for the Prevention of Neurodegenerative Diseases","volume":"69","author":"Kerdiles","year":"2017","journal-title":"Trends Food Sci. Technol."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1096\/fj.07-9677com","article-title":"Beneficial Effects of Dietary Omega-3 Polyunsaturated Fatty Acid on Toxin-Induced Neuronal Degeneration in an Animal Model of Parkinson\u2019s Disease","volume":"22","author":"Bousquet","year":"2008","journal-title":"FASEB J."},{"key":"ref_280","doi-asserted-by":"crossref","unstructured":"Singh, P.K., Gupta, M.K., and Nath, R. (2023). Omega-3 Fatty Acid as a Protectant in Lead-Induced Neurotoxicity. Treatments, Nutraceuticals, Supplements, and Herbal Medicine in Neurological Disorders, Elsevier.","DOI":"10.1016\/B978-0-323-90052-2.00002-0"},{"key":"ref_281","doi-asserted-by":"crossref","unstructured":"Joffre, C., Dinel, A.L., Chataigner, M., Pallet, V., and Lay\u00e9, S. (2020). N-3 Polyunsaturated Fatty Acids and Their Derivates Reduce Neuroinflammation during Aging. Nutrients, 12.","DOI":"10.3390\/nu12030647"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.pnpbp.2009.07.018","article-title":"Modulation of Brain-Derived Neurotrophic Factor as a Potential Neuroprotective Mechanism of Action of Omega-3 Fatty Acids in a Parkinsonian Animal Model","volume":"33","author":"Bousquet","year":"2009","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.nbd.2011.09.009","article-title":"High-Fat Diet Exacerbates MPTP-Induced Dopaminergic Degeneration in Mice","volume":"45","author":"Bousquet","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.arr.2011.03.001","article-title":"Impact of Omega-3 Fatty Acids in Parkinson\u2019s Disease","volume":"10","author":"Bousquet","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2217\/17460875.3.2.133","article-title":"Can We Prevent Parkinson\u2019s Disease with n-3 Polyunsaturated Fatty Acids?","volume":"3","author":"Calon","year":"2008","journal-title":"Future Lipidol."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1212\/01.WNL.0000166038.67153.9F","article-title":"Dietary Fatty Acids and the Risk of Parkinson Disease The Rotterdam Study","volume":"64","author":"Bornebroek","year":"2005","journal-title":"Neurology"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1093\/ajcn\/86.5.1486","article-title":"Prospective Study of Dietary Pattern and Risk of Parkinson Disease","volume":"86","author":"Gao","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.parkreldis.2013.09.023","article-title":"Dietary Fat Intake, Pesticide Use, and Parkinson\u2019s Disease","volume":"20","author":"Kamel","year":"2014","journal-title":"Park. Relat. Disord."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3233\/JAD-141305","article-title":"Tolerability and Safety of Souvenaid in Patients with Mild Alzheimer\u2019s Disease: Results of Multi-Center, 24-Week, Open-Label Extension Study","volume":"44","author":"Verhey","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_290","first-page":"1","article-title":"Effects on Transthyretin in Plasma and Cerebrospinal Fluid by Dha-Rich n-3 Fatty Acid Supplementation in Patients with Alzheimer\u2019s Disease: The Omegad Study","volume":"36","author":"Basun","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1301\/nr.2006.may.S24-S33","article-title":"Nutrition in Brain Development and Aging: Role of Essential Fatty Acids","volume":"64","author":"Uauy","year":"2006","journal-title":"Nutr. Rev."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.nutres.2025.06.005","article-title":"Multimicronutrient and Omega-3 Fatty Acid Supplementation Reduces Low-Grade Inflammation in Older Participants: An Exploratory Study","volume":"140","author":"Kerlikowsky","year":"2025","journal-title":"Nutr. Res."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"e202400752","DOI":"10.1002\/mnfr.202400752","article-title":"Immunomodulatory Effects of Omega-3 Fatty Acids: Mechanistic Insights and Health Implications","volume":"69","author":"Bodur","year":"2025","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_294","doi-asserted-by":"crossref","unstructured":"Sarparast, M., Dattmore, D., Alan, J., and Lee, K.S.S. (2020). Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration. Nutrients, 12.","DOI":"10.3390\/nu12113523"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s10522-023-10045-y","article-title":"Molecular Mechanism of Caloric Restriction Mimetics-Mediated Neuroprotection of Age-Related Neurodegenerative Diseases: An Emerging Therapeutic Approach","volume":"24","author":"Sharma","year":"2023","journal-title":"Biogerontology"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"111710","DOI":"10.1016\/j.mad.2022.111710","article-title":"Long-Term Caloric Restriction Ameliorates T Cell Immunosenescence in Mice","volume":"206","author":"Asami","year":"2022","journal-title":"Mech. Ageing Dev."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40168-022-01249-4","article-title":"Effects of Caloric Restriction on the Gut Microbiome Are Linked with Immune Senescence","volume":"10","author":"Grenkowitz","year":"2022","journal-title":"Microbiome"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1126\/science.abg7292","article-title":"Caloric Restriction in Humans Reveals Immunometabolic Regulators of Health Span","volume":"375","author":"Spadaro","year":"2022","journal-title":"Science"},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41401-020-0397-3","article-title":"Cardamonin Protects Against Lipopolysaccharide-Induced Myocardial Contractile Dysfunction in Mice Through Nrf2-Regulated Mechanism","volume":"42","author":"Tan","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1002\/ar.23781","article-title":"Resveratrol Suppresses Rotenone-induced Neurotoxicity Through Activation of SIRT1\/Akt1 Signaling Pathway","volume":"301","author":"Wang","year":"2018","journal-title":"Anat. Rec."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/ana.25250","article-title":"Age-Related Changes in the Gut Microbiota Influence Systemic Inflammation and Stroke Outcome","volume":"84","author":"Spychala","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_302","doi-asserted-by":"crossref","unstructured":"Pallikkuth, S., Mendez, R., Russell, K., Sirupangi, T., Kvistad, D., Pahwa, R., Villinger, F., Banerjee, S., and Pahwa, S. (2021). Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.748397"},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1016\/j.cmet.2021.10.010","article-title":"Microbiota-Derived Acetate Enables the Metabolic Fitness of the Brain Innate Immune System during Health and Disease","volume":"33","author":"Erny","year":"2021","journal-title":"Cell Metab."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.it.2024.01.006","article-title":"Gut-Associated Lymphoid Tissue: A Microbiota-Driven Hub of B Cell Immunity","volume":"45","author":"Bemark","year":"2024","journal-title":"Trends Immunol."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1182\/blood.2022017514","article-title":"Fecal Microbiota Transplantation from Young Mice Rejuvenates Aged Hematopoietic Stem Cells by Suppressing Inflammation","volume":"141","author":"Zeng","year":"2023","journal-title":"Blood"},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nature15367","article-title":"Neutrophil Ageing Is Regulated by the Microbiome","volume":"525","author":"Zhang","year":"2015","journal-title":"Nature"},{"key":"ref_307","doi-asserted-by":"crossref","unstructured":"Lin, S.W., Tsai, Y.S., Chen, Y.L., Wang, M.F., Chen, C.C., Lin, W.H., and Fang, T.J. (2021). Lactobacillus Plantarum Gkm3 Promotes Longevity, Memory Retention, and Reduces Brain Oxidation Stress in Samp8 Mice. Nutrients, 13.","DOI":"10.3390\/nu13082860"},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.nut.2019.02.005","article-title":"Supplementation with Bifidobacterium Longum Bar33 and Lactobacillus Helveticus Bar13 Mixture Improves Immunity in Elderly Humans (over 75 Years) and Aged Mice","volume":"63\u201364","author":"Finamore","year":"2019","journal-title":"Nutrition"},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"102563","DOI":"10.1016\/j.eclinm.2024.102563","article-title":"Safety and Efficacy of Faecal Microbiota Transplantation in Patients with Mild to Moderate Parkinson\u2019s Disease (GUT-PARFECT): A Double-Blind, Placebo-Controlled, Randomised, Phase 2 Trial","volume":"71","author":"Bruggeman","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1001\/jamaneurol.2024.2305","article-title":"Fecal Microbiota Transplantation for Treatment of Parkinson Disease","volume":"81","author":"Scheperjans","year":"2024","journal-title":"JAMA Neurol."},{"key":"ref_311","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Villodres, J.A., Escamilla, A., Mercado-S\u00e1enz, S., Alba-Tercedor, C., Rodriguez-Perez, L.M., Arranz-Salas, I., Sanchez-Varo, R., and Berm\u00fadez, D. (2023). Microbiome Alterations and Alzheimer\u2019s Disease: Modeling Strategies with Transgenic Mice. Biomedicines, 11.","DOI":"10.3390\/biomedicines11071846"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"106687","DOI":"10.1016\/j.phrs.2023.106687","article-title":"Gut Microbiota Remodeling Improves Natural Aging-Related Disorders Through Akkermansia Muciniphila and Its Derived Acetic Acid","volume":"189","author":"Ma","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_313","doi-asserted-by":"crossref","unstructured":"Ch\u00e9nard, T., Pr\u00e9vost, K., Dub\u00e9, J., and Mass\u00e9, E. (2020). Immune System Modulations by Products of the Gut Microbiota. Vaccines, 8.","DOI":"10.3390\/vaccines8030461"},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41422-020-0332-7","article-title":"Interaction between Microbiota and Immunity in Health and Disease","volume":"30","author":"Zheng","year":"2020","journal-title":"Cell Res."},{"key":"ref_315","doi-asserted-by":"crossref","unstructured":"Duan, M., Cao, R., Yang, Y., Chen, X., Liu, L., Ren, B., Wang, L., and Goh, B.C. (2024). Blood\u2013Brain Barrier Conquest in Glioblastoma Nanomedicine: Strategies, Clinical Advances, and Emerging Challenges. Cancers, 16.","DOI":"10.20944\/preprints202409.0186.v1"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"215696","DOI":"10.1016\/j.ccr.2024.215696","article-title":"Glioma Nanomedicine: Design, Fabrication and Theranostic Application","volume":"505","author":"Wu","year":"2024","journal-title":"Coord. Chem. Rev."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.3762\/bjnano.9.98","article-title":"Review on Nanoparticles and Nanostructured Materials: History, Sources, Toxicity and Regulations","volume":"9","author":"Jeevanandam","year":"2018","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"17028","DOI":"10.1039\/C3RA47370H","article-title":"Polymeric Micelles as Drug Delivery Vehicles","volume":"4","author":"Ahmad","year":"2014","journal-title":"RSC Adv."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering Precision Nanoparticles for Drug Delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_320","doi-asserted-by":"crossref","unstructured":"Sercombe, L., Veerati, T., Moheimani, F., Wu, S.Y., Sood, A.K., and Hua, S. (2015). Advances and Challenges of Liposome Assisted Drug Delivery. Front. Pharmacol., 6.","DOI":"10.3389\/fphar.2015.00286"},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13024-024-00715-x","article-title":"Rejuvenating Aged Microglia by P16ink4a-SiRNA-Loaded Nanoparticles Increases Amyloid-\u03b2 Clearance in Animal Models of Alzheimer\u2019s Disease","volume":"19","author":"Shin","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"6642","DOI":"10.1039\/D2SC01662A","article-title":"Photoinduced Elimination of Senescent Microglia Cells in Vivo by Chiral Gold Nanoparticles","volume":"13","author":"Xu","year":"2022","journal-title":"Chem. Sci."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.nano.2019.02.004","article-title":"Vitamin D-Binding Protein-Loaded PLGA Nanoparticles Suppress Alzheimer\u2019s Disease-Related Pathology in 5XFAD Mice","volume":"17","author":"Jeon","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"8171","DOI":"10.1039\/D1BM01202A","article-title":"Liposomes Loaded with Polyphenol-Rich Grape Pomace Extracts Protect from Neurodegeneration in a Rotenone-Based In Vitro Model of Parkinson\u2019s Disease","volume":"9","author":"Marino","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.nano.2014.09.015","article-title":"Repeated Intraperitoneal Injections of Liposomes Containing Phosphatidic Acid and Cardiolipin Reduce Amyloid-\u03b2 Levels in APP\/PS1 Transgenic Mice","volume":"11","author":"Re","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"20019","DOI":"10.1038\/srep20019","article-title":"Intrathecal Delivery of Frataxin MRNA Encapsulated in Lipid Nanoparticles to Dorsal Root Ganglia as a Potential Therapeutic for Friedreich\u2019s Ataxia","volume":"6","author":"Nabhan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1093\/brain\/awad014","article-title":"Multifaceted Nanoparticles: Emerging Mechanisms and Therapies in Neurodegenerative Diseases","volume":"146","author":"Mistretta","year":"2023","journal-title":"Brain"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/8\/657\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T04:15:04Z","timestamp":1775880904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/8\/657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":327,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cells15080657"],"URL":"https:\/\/doi.org\/10.3390\/cells15080657","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]}}}