Abstract
Aging is intimately associated with multisystem functional decline and an increased risk of chronic diseases. A pivotal cytological basis underlying this process is the progressive dysregulation of the mitochondrial quality control (MQC) network. Emerging evidence suggests that MQC is not a singular process but rather a multitiered synergistic system encompassing mitochondrial biogenesis, dynamic remodeling, selective autophagy (mitophagy), proteostasis maintenance, and coordinated mitochondrial-organelle communication. This integrated network is critical for preserving cellular energy homeostasis, redox balance, and stress tolerance. During aging, impairments in mitochondrial genomic coordination, network topology, autophagic flux, and protein import and folding collectively contribute to bioenergetic decline, chronic low-grade inflammation, and metabolic imbalance. As a safe and sustainable nonpharmacological intervention, regular exercise systematically remodels MQC structure and function by integrating signaling axes such as AMPK, SIRT1, and p38 MAPK, thereby promoting coordinated mitochondrial renewal and partially reversing aging-associated mitochondrial dysfunction. On the basis of a systematic elucidation of the core mechanisms of MQC and its dysregulation during aging, this review highlights the differential regulatory effects of distinct exercise modalities-specifically endurance training, high-intensity interval training (HIIT), and resistance training-on mitochondrial dynamics, autophagic flux, proteostasis, and mitochondrial turnover. Furthermore, the intrinsic associations among exercise-MQC coupling, inflammatory responses, metabolic imbalances, and emerging peripheral biomarkers are explored. Finally, current research limitations and challenges in clinical translation are analyzed, and future research directions regarding dose-response relationships, multimodal exercise prescriptions, personalized strategies, and systemic integrated regulation are proposed. This review aims to provide a refined theoretical basis for optimizing exercise-based anti-aging interventions.