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Considering that mitochondria are involved in a multitude of cellular processes, mitochondrial dysfunction has been shown to play a role within several age-related diseases, including cancers, diabetes (type 2), and neurodegenerative diseases, although the underlying mechanisms are not entirely understood. The significant increase in lifespan and increased incidence of age-related diseases over recent decades has confirmed the necessity to understand the mechanisms by which mitochondrial dysfunction impacts the process of aging and age-related diseases. In this review, we will offer a brief overview of mitochondria, along with structure and function of this important organelle. We will then discuss the cause and consequence of mitochondrial dysfunction in the aging process, with a particular focus on its role in inflammation, cognitive decline, and neurodegenerative diseases, such as Huntington\u2019s disease, Parkinson\u2019s disease, and Alzheimer\u2019s disease. We will offer insight into therapies and interventions currently used to preserve or restore mitochondrial functioning during aging and neurodegeneration.<\/jats:p>","DOI":"10.3390\/cimb46030130","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T05:31:19Z","timestamp":1709616679000},"page":"1987-2026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases"],"prefix":"10.3390","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2904-3883","authenticated-orcid":false,"given":"Sydney","family":"Bartman","sequence":"first","affiliation":[{"name":"George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA"},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Coppotelli","sequence":"additional","affiliation":[{"name":"George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA"},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3879-4817","authenticated-orcid":false,"given":"Jaime M.","family":"Ross","sequence":"additional","affiliation":[{"name":"George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA"},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.15252\/embr.201439518","article-title":"Living Too Long","volume":"16","author":"Brown","year":"2015","journal-title":"EMBO Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"643254","DOI":"10.3389\/fphar.2021.643254","article-title":"Neurodegenerative Disease and the NLRP3 Inflammasome","volume":"12","author":"Holbrook","year":"2021","journal-title":"Front. 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