Mitochondrial biogenesis is the process by which existing mitochondria grow and divide, essential for cellular energy production. This process is regulated by various molecular mechanisms, including the PGC-1α coactivator, which activates transcription factors like NRF-1 and NRF-2, leading to the expression of mitochondrial genes. PGC-1α is regulated by factors such as AMPK, which senses cellular energy status and promotes mitochondrial biogenesis. AMPK activity decreases with age, contributing to reduced mitochondrial function and increased disease risk. Other regulators include CaMKIV, NO, SIRT1, and TORC1, which also influence mitochondrial biogenesis through different pathways. Exercise and caloric restriction enhance mitochondrial biogenesis by activating these regulators. Mitochondrial dysfunction is linked to aging and diseases like Type 2 diabetes and Alzheimer's. Understanding these regulatory mechanisms could lead to new therapeutic strategies for mitochondrial-related disorders. Drugs like TZDs and metformin also influence mitochondrial biogenesis, highlighting the importance of these pathways in metabolic health. Caloric restriction improves mitochondrial function and energy efficiency, suggesting its potential as a therapeutic approach. Overall, mitochondrial biogenesis is a complex process regulated by multiple factors, and understanding these mechanisms is crucial for addressing mitochondrial dysfunction in aging and disease.Mitochondrial biogenesis is the process by which existing mitochondria grow and divide, essential for cellular energy production. This process is regulated by various molecular mechanisms, including the PGC-1α coactivator, which activates transcription factors like NRF-1 and NRF-2, leading to the expression of mitochondrial genes. PGC-1α is regulated by factors such as AMPK, which senses cellular energy status and promotes mitochondrial biogenesis. AMPK activity decreases with age, contributing to reduced mitochondrial function and increased disease risk. Other regulators include CaMKIV, NO, SIRT1, and TORC1, which also influence mitochondrial biogenesis through different pathways. Exercise and caloric restriction enhance mitochondrial biogenesis by activating these regulators. Mitochondrial dysfunction is linked to aging and diseases like Type 2 diabetes and Alzheimer's. Understanding these regulatory mechanisms could lead to new therapeutic strategies for mitochondrial-related disorders. Drugs like TZDs and metformin also influence mitochondrial biogenesis, highlighting the importance of these pathways in metabolic health. Caloric restriction improves mitochondrial function and energy efficiency, suggesting its potential as a therapeutic approach. Overall, mitochondrial biogenesis is a complex process regulated by multiple factors, and understanding these mechanisms is crucial for addressing mitochondrial dysfunction in aging and disease.