Mitochondrial homeostasis in bone aging: Unraveling dysfunctional pathways and developing precision therapies

Mitochondria have complex functional and information-processing networks that play key roles in both health regulation and disease progression. However, the multiple properties and complex thresholds of mitochondrial dysfunction and quality control make the contribution of mitochondria to bone aging elusive. These factors prevent mitochondria from being among the most important precision therapies. Currently, many strategies that target mitochondrial homeostasis have entered clinical trials. In mitochondria, mitochondrial DNA (mtDNA) and its associated proteins are potential therapeutic agents for immunometabolic diseases and tissue injury, with the aim of enhancing mitochondrial function. Here, we comprehensively review the intrinsic mechanisms of mitochondrial dysfunction and quality control leading to bone aging and summarize current strategies for the treatment of skeletal aging disorders and the clinical translation of relevant agents in terms of unraveling dysfunctional pathways and developing precision therapies. In this review, we offer a general overview of the progress of clinical application in the treatment of skeletal senescence diseases, and we also provide prospects for the challenges associated with the role of mitochondrial dysfunction in bone senescence in clinical application and future trends in this field.