This chapter summarizes how autophagy is regulated by epigenetic mechanisms and how neuroinflammation plays a role in neurodegenerative diseases. This could be the secret to creating fresh approaches to the diagnosis and management of age-related brain disorders. According to recent studies, epigenetic instability can cause neuroinflammation by triggering pathways such as the microglial NLRP3 inflammasome. It can alter genes like ATG5 and BECN1 that promote autophagy. A vicious cycle that damages neurons and accelerates cognitive decline is produced by this effect. We review how chromatin structure, DNA alterations, and regulatory RNAs impact brain processes like microglial behavior, protein balance, neuron survival, and inflammation regulation. We also go over promising treatments that target these epigenetic changes, such as RNA-based therapies, CRISPR/dCas9-based gene editing, and modulators of histone deacetylases and histone acetyltransferases. We may be able to slow or even reverse neurodegeneration in ageing brains by comprehending and reprogramming the epigenetic connections between autophagy and neuroinflammation. This chapter provides a road map for creating multimodal interventions by connecting mechanistic insights with cutting-edge therapeutic approaches.