Aging can lead to senescence of stromal cells in parallel with CAF activation, chronic inflammation and increased MMP production with matrix remodeling. As discussed in the text, the NF-κB, AP1, Nrf2 and Notch/CSL signaling pathways have been implicated in one or more of these processes. Autophagy can delay or limit the negative consequences of tissue / organismal aging (A) while, at the same time, playing a more direct positive role in stromal cell senescence (B). Senescence of stromal cells is linked to CAF activation and chronic inflammation, while, in epithelial cells, it functions in concert with differentiation as intrinsic tumor suppressing mechanism.