Deciphering the interplay between mitophagy, epigenetic regulation, and neurodegeneration in ageing

The ""MitoEpigeNeAge"" research proposal seeks to uncover the molecular mechanisms of age-related neurodegeneration by focusing on the interplay between mitophagy, redox-regulated histone methylation, and neuronal death. Brain ageing is characterized by the accumulation of damaged mitochondria and epigenetic changes, leading to neurodegeneration. Mitophagy, the process that clears damaged mitochondria, declines with age but extends lifespan and offers neuroprotection when activated. However, its impact on the epigenome remains unclear. The project will utilize Caenorhabditis elegans due to its well-defined nervous system and evolutionary conservation of neuronal ageing mechanisms. Advanced technologies will analyse chromatin accessibility and gene expression in redox-sensitive neurons. Super-resolution imaging and optogenetics will allow precise manipulation of mitochondrial damage and mitophagy in live animals. Key objectives include: 1) Monitoring chromatin accessibility, histone methylation, and gene expression in wild-type and mitophagy-deficient worms