ABSTRACT To cure age-related diseases is of critical importance for the life quality of elderly people. One promising strategy is to slow down aging or reverse aging with regenerative medicine. However, the regenerative capacity of stem cells and their supportive microenvironments are drastically impaired in old age. Hence, to rejuvenate functions of aged adult stem cells and their microenvironments or to maintain the youthful functions of adult stem cells in old age are critical research directions to empower regenerative medicine to fight age-associated diseases. Here, we propose to use a cutting-edge spatial transcriptomics method, Seq-Scope, to comprehensively examine the aging, regeneration and rejuvenation of eye progenitor cells and their niche cells in the sexual planarians, a champion of tissue regeneration. We aim to determine the molecular pathways that facilitate regeneration and rejuvenation in old age. The proposed experiments will define datasets of fundamental importance in the identification of niche cells and changes in aging and regeneration that will fuel long-term mechanistic studies.