The review highlights the dual role that the conserved master regulator FoxO has in aging by coordinating both stem cell proliferation and antimicrobial peptides, effector molecules of the innate immune system. As observed in non-senescent Hydra, continuously high activity of the transcription factor FoxO contributes to continuous stem cell proliferation and could support robust colonization of epithelia with a stable microbiome. The integration of research from stem cell biology, microbiology and ecology into aging concepts (Eco-Aging) acknowledges the multi-organismic nature of all living beings and presents a new conceptual framework for explaining the process of aging.