Senescence in Health and Disease Shenghui He, Norman E. Sharpless  Cell  Volume 169, Issue 6, Pages 1000-1011 (June 2017) DOI: 10.1016/j.cell.2017.05.015 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Characteristics of Cellular Senescence Senescent cells exhibit durable growth arrest, increased expression of the products of the CDKN2A locus (p16INK4a and to a lesser extent ARF), and characteristic changes in cellular structures and protein expressions (e.g., elaboration of SASP factors). Senescent cells in vitro exhibit changes in cellular morphology (e.g., increased cell spreading) and increased SA-β-galactosidase activity, but these markers have been less useful for in vivo recognition. Several other markers (e.g., short telomeres; DNA segments with chromatin alterations reinforcing senescence [DNA-SCARS]; activated NF-κB and DNA damage response; senescence-associated heterochromatin foci [SAHFs]) are often associated with cellular senescence, but these markers are neither sensitive nor specific for the senescent state. Loss of the Lamin B1 is an interesting, new marker of senescence that is under investigation. Cell 2017 169, 1000-1011DOI: (10.1016/j.cell.2017.05.015) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 2 Mechanisms of Senescent Cell Accumulation with Aging The rate at which senescent cells accumulate increases with aging. This may reflect an increased rate of senescent cell production due to changes in DNA repair, telomere dysfunction, and/or decreased senescent cell clearance by immune system. It has also been suggested that senescent cells can induce the formation of other senescent cells in a paracrine manner. Cell 2017 169, 1000-1011DOI: (10.1016/j.cell.2017.05.015) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 3 Beneficial Roles of Cellular Senescence Senescence affords tumor suppression in a cell-intrinsic manner and perhaps also by augmenting local anti-tumor immunity. The activation of the CDKN2A locus appears to limit the size of atherosclerotic plaques, thereby reducing anatomic obstruction. Senescence resulting from p21CIP expression during embryogenesis may be required for certain aspects of fetal development. Senescence contributes to wound healing and host immunity. Cell 2017 169, 1000-1011DOI: (10.1016/j.cell.2017.05.015) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 4 Detrimental Effects of Senescent Cells The accumulation of senescent cells can lead to anatomic lesions (e.g., as in an atherosclerotic plaque). The loss of replicative capacity of certain senescent cells (e.g., T cells, pancreatic β cells) may lead to defects in tissue regeneration. The occupancy of prized physiological niches by senescent cells may impair tissue homeostasis. The paracrine and endocrine elaboration of pro-inflammatory hormones and enzymes promotes tissue dysfunction locally and at the organismal level. Cell 2017 169, 1000-1011DOI: (10.1016/j.cell.2017.05.015) Copyright © 2017 Elsevier Inc. Terms and Conditions