Genetic research into ageing, longevity and late-onset disease is becoming increasingly common. Yet, there is a paucity of knowledge related to clinical actionability and the return of pathogenic variants to otherwise healthy elderly individuals. Whether or not genetic research in the elderly should be managed differently from standard practices adapted for younger populations has not yet been defined. In this article, we provide an overview of ethical and practical challenges in preparing for a genetic study of over 14 000 healthy (...) Australians aged 70 years or older enrolled in the ASPirin in Reducing Events in the Elderly Healthy Ageing Biobank. At the time of consent, all participants in this study were free of life-threatening illness, cardiovascular disease or cognitive impairment. ASPREE is thus a cohort of healthy elderly individuals with seemingly minimal burden of genetic disease recruited without ascertainment bias. The cohort presents a unique opportunity to address the penetrance of known pathogenic variants in a population without disease symptoms; however, it also raises a number of ethical concerns regarding the interpretation and disclosure of variants with known clinical actionability. Some of the challenges include how to manage the interpretation, disclosure and actioning of pathogenic variants found in otherwise healthy elderly adults without disease symptoms, whether or not to disclose findings for the benefit of family members rather than elderly consented donors themselves, how to manage the return of genetic findings to the elderly individuals who are now in severe cognitive decline or terminal illness, how to ensure quality of information and clinical service upon disclosure of results to this demographic and how to prepare for the insurance implications of disclosing genetic information under Australian law. We discuss these and other dilemmas and propose a defensible plan of management. Trial registration number ISRCTN83772183. (shrink)