{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:03:33Z","timestamp":1792789413267,"version":"4.5.0"},"reference-count":164,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Kebangsaan Malaysia Medical Centre","award":["FF-2025-210"],"award-info":[{"award-number":["FF-2025-210"]}],"id":[{"id":"https:\/\/ror.org\/01590nj79","id-type":"ROR","asserted-by":"crossref"}]},{"award":["FF-2025-210"],"award-info":[{"award-number":["FF-2025-210"]}],"id":[{"id":"https:\/\/ror.org\/01590nj79","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Brain aging is a major risk factor for neurodegenerative disorders and is associated with a progressive loss of neuronal homeostasis. Rather than resulting from a single pathological event, brain aging involves coordinated changes across multiple biological processes, including neuroinflammation, proteostasis impairment, mitochondrial dysfunction, neurotransmission deficit, cellular senescence, gut microbiota dysbiosis, extracellular vesicle dysregulation, nutrient-sensing disturbances, and metabolic drift. These processes interact across molecular, cellular, and systemic levels and may progressively increase neuronal vulnerability to neurodegenerative pathology. Age-related biological alterations may increase susceptibility to Alzheimer\u2019s disease and Parkinson\u2019s disease. Disease-associated proteins, including amyloid-\u03b2, tau, and \u03b1-synuclein, may interact with age-related inflammation, metabolic dysfunction, and loss of proteostasis. This review examines the evidence supporting these mechanisms, their interactions, and their relevance to normal brain aging, Alzheimer\u2019s disease, and Parkinson\u2019s disease. Because much of the current mechanistic evidence derives from animal and cellular models, further longitudinal and human studies are needed to provide a more complete understanding of how these mechanisms operate during human brain aging and neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms27188426","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of Brain Aging and Their Links to Alzheimer\u2019s and Parkinson\u2019s Disease Pathology"],"prefix":"10.3390","volume":"27","author":[{"given":"Haiyi","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haimeng","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1757-3780","authenticated-orcid":false,"given":"Jo Aan","family":"Goon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5239-6196","authenticated-orcid":false,"given":"Suzana","family":"Makpol","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-0581","authenticated-orcid":false,"given":"Jen Kit","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s13195-025-01861-0","article-title":"Ap1s1 Reduction in the Aging Brain Heightens Neuronal Vulnerability to Amyloid-\u03b2 and Oxidative Stress in Alzheimer\u2019s Pathogenesis","volume":"17","author":"Yang","year":"2025","journal-title":"Alzheimers Res. 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