Mitochondria-driven inflammation: a new frontier in ovarian ageing

Ovarian ageing is a key factor in the decline of female fertility. It is primarily characterised by diminished oocyte quality, follicular depletion, and dysregulated hormone levels. In recent years, mitochondria-driven inflammation has emerged as a potential mechanism in ovarian ageing. Mitochondrial dysfunction results in the accumulation of reactive oxygen species (ROS) and the release of mitochondrial DNA (mtDNA), as well as the leakage of mitochondrial components and metabolites into the cytosol or extracellular space. These elements act as damage-associated molecular patterns (DAMPs), activating inflammasomes like NLRP3, thereby initiating and amplifying innate immune responses and contributing to sustained inflammation. Furthermore, an imbalance in mitochondrial quality control mechanisms can worsen the spread and persistence of inflammatory responses. In this study, we present a comprehensive overview of the signalling origins, molecular mechanisms of amplification, and key regulatory nodes involved in mitochondria-driven inflammation during ovarian ageing. Finally, we summarise potential therapeutic strategies targeting mitochondria-driven inflammation, offering novel perspectives and targets for delaying ovarian ageing and enhancing female reproductive health.