The ‘stem-cell theory’ of ageing posits that the functional decline in adult stem cells is one of the factors contributing to ageing. Importantly, the number of stem cells does not diminish with age in many tissues but rather there are intrinsic and extrinsic changes that affect their functionality. Is it possible to reverse these changes? Experiments in the emerging model Macrostomum lignano suggest that this is indeed the case. Remarkably, induced regeneration in this animal leads to extended lifespan: repeated amputation, followed by regeneration, results in animals that live far beyond the median lifespan of 205 days. Regeneration in M. lignano is facilitated by stem cells called neoblasts, and it appears that regeneration resets the ‘ageing program’ in these animals.Due to its high regeneration capacity, small size, transparency and clear morphology, ease of culture, short generation time and amenability to genetic manipulation, M. lignano has great potential as a model organism for stem cell research. I have recently started developing genomic and genetic tools and resources for this model, and at present my group has generated a draft genome assembly, produced de novo transcriptome assembly, discovered several neoblast marker genes and made the first stable transgenic lines in this animal.Here I propose to study molecular mechanisms underlying rejuvenation in M. lignano, and to further advance M. lignano as a model organism through development of missing genetic tools and resources. I will address how young, aged and regenerated worms differ in their gene and small RNA expression profiles, and what are the differences and variation levels between neoblasts of young, old and regenerated animals. The biological roles of the identified candidate genes and their effects on the lifespan and neoblast activity will be investigated. In parallel, methods for efficient transgenesis and gene manipulation will be developed, and the genome annotation improved.