Research Progress on the Pathogenic Mechanisms of Mitochondria in Aging-Related Diseases

Population aging has become a global public health challenge, and the high incidence and progression of aging-related diseases seriously reduce the quality of life and increase the burden of disease in the elderly population. As the core organelle of cellular energy metabolism, mitochondria are involved in oxidative phosphorylation, substance metabolism, signal transduction, and cell fate regulation, and their structural integrity and functional stability are the key to maintain the normal physiological state of the body. In recent years, a large number of studies have confirmed that mitochondrial dysfunction is a core driver of the aging process and the onset and development of aging-related diseases. Its molecular mechanisms involve oxidative stress imbalance, energy metabolism disorders, impaired mitochondrial quality control, and abnormal mitochondrial-nuclear communication. Excessive production of reactive oxygen species and accumulation of mitochondrial DNA mutations can trigger a cascade of oxidative damage, leading to the destruction of biological macromolecular structure and function. Insufficient ATP production, abnormal accumulation of metabolic intermediates, and disruptions of energy pathways such as AMPK/mTOR further exacerbate cellular metabolic collapse. Mitochondrial bioattenuation, fusion-division imbalance, and PINK1/Parkin-mediated mitochondrial autophagy defects together lead to damaged mitochondrial clearance disorders and abnormal mitochondrial accumulation. Abnormal mitochondrial function is widely involved in the pathological process of various aging-related diseases such as Alzheimer's disease, Parkinson's disease, heart failure, type 2 diabetes, non-alcoholic fatty liver disease, and cancer. Based on the above mechanisms, emerging strategies such as calorie restriction, exercise intervention, mitochondria-targeted antioxidants, biogenesis activators, mitochondrial autophagy modulators, mitochondrial transplantation, and gene editing provide important directions for delaying aging and preventing aging-related diseases. This paper systematically reviews the core molecular mechanisms of mitochondrial dysfunction, summarizes its role in typical aging-related diseases, and discusses the research progress of mitochondrial targeting interventions. It aims to provide a theoretical basis and idea reference for the elucidating aging mechanisms and developing new intervention strategies.