Table 1.
The senescence-associated secretory phenotype (SASP). Factors significantly altered between presenescent and senescent states are listed
| SASP factorsa | Secretory profile of senescent cellsb |
Changes in the SASP due to the loss of p53 and/or gain of oncogenic RAS |
|---|---|---|
| Soluble factors | ||
| Interleukins (IL) | ||
| IL-6 | ↑ | ↑ |
| IL-7 | ↑ | ↑ |
| IL-1a, -1b | ↑ | ↑ |
| IL-13 | ↑ | ↑ |
| IL-15 | ↑ | ↑ |
| Chemokines (CXCL, CCL) | ||
| IL-8 | ↑ | ↑ |
| GRO-a,-b,-gc | ↑ | ↑ |
| MCP-2 | ↑ | ↑ |
| MCP-4 | ↑ | × |
| MIP-1a | ↑ | ↑ |
| MIP-3a | ↑ | × |
| HCC-4 | ↑ | × |
| Eotaxin | × | ↑ |
| Eotaxin-3 | ↑ | ↑ |
| TECK | × | ↑ |
| ENA-78 | × | ↑ |
| I-309 | × | ↑ |
| I-TAC | × | ↓ |
| Other inflammatory factors | ||
| GM-CSE | ↑ | ↑ |
| G-CSE | × | ↑ |
| IFN-γ | × | ↑ |
| BLC | × | ↑ |
| MIF | ↑ | ↓ |
| Growth factors and regulators | ||
| Amphiregulin | ↑ | × |
| Epiregulin | ↑ | × |
| Heregulin | ↑ | × |
| EGF | ↑ or × | ↑ |
| bFGF | ↑ | ↑ |
| HGF | ↑ | × |
| KGF (FGF7) | ↑ | ↑ |
| VEGF | ↑ | × |
| Angiogenin | ↑ | × |
| SCF | ↑ | × |
| SDF-1 | ↑ or × | ↑ |
| PIGF | ↑ | × |
| NGF | × | ↓ |
| IGFBP-2, -3, -4, -6, -7 | ↑ | ↑ or × |
| Proteases and regulators | ||
| MMP-1, -3, -10, -12, -13, -14 | ↑ | ↑ or × |
| TIMP-1 | ↓ or × | × |
| TIMP-2 | ↑ | × |
| PAI-1, -2; tPA; uPA | ↑ | × |
| Cathepsin B | ↑ | × |
| Soluble or shed receptors or ligands | ||
| ICAM-1, -3 | ↑ | × |
| OPG | ↑ | ↑ |
| sTNFRI | ↑ | × |
| TRAIL-R3, Fas, sTNFRII | ↑ | × |
| Fas | ↑ | × |
| uPAR | ↑ | ↑ |
| SGP130 | ↑ | ↑ |
| EGF-R | ↑ | × |
| Nonprotein soluble factors | ||
| PGE2 | ↑ | − |
| Nitric oxide | ↑ | − |
| Reactive oxygen species | Altered | − |
| Insoluble factors (ECM) | ||
| Fibronectin | ↑ | − |
| Collagens | Altered | − |
| Laminin | Altered | − |
Factors are arranged by family.
The secretory changes that occur at senescence are indicated by upward arrows (increase), crosses (no change), and downward arrows (decrease). Loss of p53 or gain of oncogenic RAS increases (upward arrows) or decreases (downward arrows) the secretion of several SASP factors.
Abbreviations: bFGF, basic fibroblast growth factor; ECM, extracellular matrix; EGF, endothelial growth factor; GRO, growth-related oncogene; HGF, hepatocyte growth factor; ICAM, intercellular adhesion molecule; IGFBP, insulin-like growth factor\p=n-\binding protein; MCP, membrane cofactor protein; MMP, matrix metalloproteinase; NGF, nerve growth factor; OPG, osteoprotegerin; PAI, plasminogen activator inhibitor; PGE2, prostaglandin E2; PIGF, placental growth factor; SCF, stem cell factor; SDF, stromal cell\p=n-\derived factor; sTNFR, soluble tumor necrosis factor receptor; t-PA, tissue-type plasminogen activator; TIMP, tissue inhibitor of metalloproteinases; TRAIL, tumor necrosis factor\p=n-\related apoptosis-inducing ligand; u-PA, urokinase-type plasminogen activator; uPAR, u-PA receptor; VEGF, vascular endothelial growth factor.