Mitochondria, which became incorporated into eukaryotic cells about 2 billion years ago, play a crucial role in various cellular processes such as energy production, calcium buffering, homeostasis, steroid synthesis, cell growth, apoptosis, inflammation, and ROS production. Mitochondrial dysfunction has been implicated in several age-related diseases, including cancers, diabetes (type 2), and neurodegenerative diseases. The review provides an overview of mitochondria, their structure, and function, and discusses the causes and consequences of mitochondrial dysfunction in aging, with a focus on its role in inflammation, cognitive decline, and neurodegenerative diseases. It also explores current therapies and interventions aimed at preserving or restoring mitochondrial function during aging and neurodegeneration. Key points include: - Mitochondrial dysfunction is a primary hallmark of aging and is central to the Mitochondrial Theory of Aging. - Mitochondria regulate energy production, calcium signaling, apoptosis, and biosynthetic pathways. - Causes of mitochondrial dysfunction include reactive oxygen species (ROS), mtDNA mutations, reduced mitochondrial biogenesis, and impaired mitophagy. - Mitochondrial dysfunction contributes to chronic inflammation, a key feature of aging and age-related diseases. - In the brain, mitochondrial dysfunction leads to morphological and functional changes, cognitive decline, and increased susceptibility to neurodegenerative diseases. - Specific disorders, such as Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease, are highlighted for their association with mitochondrial dysfunction. The review emphasizes the importance of understanding mitochondrial dysfunction in aging and age-related diseases to develop effective therapeutic strategies.Mitochondria, which became incorporated into eukaryotic cells about 2 billion years ago, play a crucial role in various cellular processes such as energy production, calcium buffering, homeostasis, steroid synthesis, cell growth, apoptosis, inflammation, and ROS production. Mitochondrial dysfunction has been implicated in several age-related diseases, including cancers, diabetes (type 2), and neurodegenerative diseases. The review provides an overview of mitochondria, their structure, and function, and discusses the causes and consequences of mitochondrial dysfunction in aging, with a focus on its role in inflammation, cognitive decline, and neurodegenerative diseases. It also explores current therapies and interventions aimed at preserving or restoring mitochondrial function during aging and neurodegeneration. Key points include: - Mitochondrial dysfunction is a primary hallmark of aging and is central to the Mitochondrial Theory of Aging. - Mitochondria regulate energy production, calcium signaling, apoptosis, and biosynthetic pathways. - Causes of mitochondrial dysfunction include reactive oxygen species (ROS), mtDNA mutations, reduced mitochondrial biogenesis, and impaired mitophagy. - Mitochondrial dysfunction contributes to chronic inflammation, a key feature of aging and age-related diseases. - In the brain, mitochondrial dysfunction leads to morphological and functional changes, cognitive decline, and increased susceptibility to neurodegenerative diseases. - Specific disorders, such as Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease, are highlighted for their association with mitochondrial dysfunction. The review emphasizes the importance of understanding mitochondrial dysfunction in aging and age-related diseases to develop effective therapeutic strategies.