Figure 3. Intrinsic / extrinsic aging of tissue stem cells. Based on the body of published literature, gene expression, epigenome, signal transduction and behavior of stem cells are influenced by the signals that emanate from their local and systemic niches. Niche cells experience intrinsic aging, which results in the changed extrinsic influences on tissue stem cells. Accordingly, in addition to gene therapy and not adding stem cells, defined molecular approaches for enhancement of tissue maintenance and repair have been demonstrated .