Ageing is emerging as a universal problem bringing formidable socioeconomic challenges. Studies on the mechanisms of ageing will facilitate our understanding of the process and will generate potential preventive strategies. Since no single ageing theory can satisfactorily explain all aspects of the ageing process, an integration of multiple theories on ageing is favored. The speaker will describe his latest studies on how two classical ageing hypotheses, persistent DNA damage and mitochondrial dysfunction, converge to explain premature ageing symptoms and contribute to neurological phenotypes in a series of ageing laboratory models. Emerging evidence suggests a critical role for DNA damage signalling from the nucleus to mitochondria (NM signalling) in regulating mitochondrial function and ageing. The interconnected roles of DNA damage, NAD+, and mitophagy will be explored in relation to ageing and neurodegenerative diseases, especially Alzheimer’s disease.