Hematopoietic stem cells (HSCs) from young and aged mice differ in their activity, and these differences in the activity are mostly intrinsic to HSCs. We therefore refer to aged HSCs and young HSCs when we speak of stem cells from aged and young animals. What are the molecular and cellular mechanisms that separate young HSCs from aged HSCs? Cell-cell interactions of HSCs with stroma cells in the stem cell niche are considered to be central for stem cell self-renewal as well as differentiation. We recently published data indicating that aged primitive hematopoietic cells are less adhesive to stroma cells when compared to young cells and that this altered interaction might be due to elevated activity of the small RhoGTPase Cdc42 in aged cells. In this manuscript we thus propose a novel model for stem cell aging: aged primitive hematopoietic cells are impaired in their ability to interact efficiently with stroma cells, which might result in the reduced self-renewal capacity as well as altered differentiation ability associated with aged stem cells.