Volume 36, Issue 1, Pages 2-14 (October 2009) Healing and Hurting: Molecular Mechanisms, Functions, and Pathologies of Cellular Senescence  Peter D. Adams  Molecular Cell  Volume 36, Issue 1, Pages 2-14 (October 2009) DOI: 10.1016/j.molcel.2009.09.021 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 Established Triggers, Signals, and Effectors of Cell Senescence Signaling pathways restricted to mouse or human, or more dominant in one species over the other, are indicated. Dashed lines are links that are poorly defined mechanistically. See text for details. Molecular Cell 2009 36, 2-14DOI: (10.1016/j.molcel.2009.09.021) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 2 Emerging Senescence Signaling Pathways Recently defined and/or more speculative signaling pathways that drive senescence. Different signals appear to specifically regulate different components of the senescent phenotype (yellow box). Green arrows indicate activation of one signal/effector by another. Red indicates inhibition. See text for details. Molecular Cell 2009 36, 2-14DOI: (10.1016/j.molcel.2009.09.021) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 3 Senescence as a Tumor Suppressor Mechanism Acquisition of an activated oncogene or inactivation of a tumor suppressor initially causes a proliferative burst. Ultimately, senescence kicks in to arrest proliferation of the cells harboring the oncogenic event. Proliferation arrest is reinforced through the secretome. Senescence-associated proliferation arrest is likely to arrest tumor progression by preventing proliferation of neoplastic cells and suppressing accumulation of additional genetic alterations (genome stability). In addition, senescence recruits the innate immune system to clear the genetically altered cells that threaten the host with malignant disease. See text for details. Molecular Cell 2009 36, 2-14DOI: (10.1016/j.molcel.2009.09.021) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 4 Healing and Hurting Cancer-causing genetic alterations and tissue wounding activate cell senescence. The senescence response heals the tissue, in part by crosstalking to other cell types, e.g., the immune system, through its inflammatory secretome. Ultimately, senescence can perhaps hurt the tissue, thereby driving degenerative diseases and cancers of aging. See text for details. Molecular Cell 2009 36, 2-14DOI: (10.1016/j.molcel.2009.09.021) Copyright © 2009 Elsevier Inc. Terms and Conditions