Contributors |
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xv | |
Foreword |
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xxi | |
Part 1 Fundamentals |
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Chapter 1 Cellular senescence: from old to new testament |
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3 | (26) |
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Old testament-genesis of senescence |
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3 | (4) |
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New testament-from mechanisms and roles of senescence to therapies |
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7 | (12) |
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Replicative senescence and telomeres |
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7 | (1) |
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Oncogene-induced senescence and tumor suppression |
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7 | (3) |
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Damage-induced senescence |
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10 | (1) |
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Hallmarks of cellular senescence |
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10 | (1) |
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11 | (1) |
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Senescence in physiology, repair, and embryonic development |
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12 | (2) |
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Senescence in aging and age-related disorders |
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14 | (1) |
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Prosenescent and antisenescent therapies |
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15 | (3) |
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18 | (1) |
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19 | (10) |
Part 2 Cellular senescence in disease states |
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Chapter 2 Premalignant lesions and cellular senescence |
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29 | (32) |
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29 | (4) |
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Cellular senescence in premalignant lesions: evidence in various organs |
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33 | (14) |
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36 | (2) |
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38 | (1) |
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39 | (1) |
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40 | (2) |
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42 | (1) |
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43 | (1) |
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44 | (1) |
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45 | (1) |
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46 | (1) |
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47 | (1) |
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47 | (1) |
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48 | (1) |
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48 | (11) |
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59 | (2) |
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Chapter 3 Lung aging and senescence in health and disease |
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61 | (20) |
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Fernanda Hernandez-Gonzalez |
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61 | (2) |
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Normal lung development and aging |
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63 | (1) |
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A brief introduction to COPD and IPF |
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64 | (1) |
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Abnormal hallmarks of lung aging in COPD and IPF |
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65 | (6) |
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65 | (3) |
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Mitochondrial dysfunction |
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68 | (1) |
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69 | (1) |
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69 | (1) |
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Epigenetic changes and miRNAs |
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70 | (1) |
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Loss of protein homeostasis (proteostasis) |
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70 | (1) |
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Deregulated nutrient sensing |
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70 | (1) |
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Extracellular matrix (ECM) dysregulation |
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71 | (1) |
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Future treatment targeting lung senescence |
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71 | (2) |
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73 | (1) |
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74 | (1) |
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74 | (1) |
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75 | (6) |
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Chapter 4 Cell senescence in pulmonary hypertension |
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81 | (26) |
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81 | (1) |
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Pulmonary hypertension, a non-aging-related proliferative vascular disorder at the crossroads of vascular disease and cancer |
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82 | (2) |
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General considerations about aging of the systemic and pulmonary vascular systems |
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84 | (1) |
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Considerations about constitutive cells of pulmonary vessels and the specificity of the pulmonary vasculature |
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85 | (1) |
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Potential mechanisms accounting for cell senescence in PH and PAH |
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86 | (6) |
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DNA damage is associated with PH |
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86 | (2) |
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Alteration in the BMPR2/TGF beta pathway |
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88 | (1) |
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89 | (1) |
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90 | (1) |
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91 | (1) |
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91 | (1) |
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92 | (1) |
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Role for senescent cells in PH and PAH |
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92 | (5) |
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92 | (2) |
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Induction of lung cell senescence: effect on PH |
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94 | (1) |
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94 | (1) |
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Prevention or protection against lung cell senescence: effect on PH |
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95 | (2) |
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97 | (1) |
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98 | (9) |
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Chapter 5 Liver diseases fibrosis and cirrhosis |
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107 | (48) |
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Liver structure and function |
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107 | (3) |
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110 | (2) |
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Liver diseases-epidemiology and clinical aspects |
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112 | (4) |
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Senescence during aging of the healthy liver |
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116 | (2) |
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Senescence in acute liver injury |
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118 | (11) |
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Senescence in chronic liver disease |
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129 | (5) |
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Role of senescence in hepatic dysfunction |
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134 | (1) |
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Evolutionary role of senescence in the liver |
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135 | (2) |
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Senescence during hepatic carcinogenesis |
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137 | (5) |
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Summary and closing comments |
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142 | (1) |
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143 | (12) |
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Chapter 6 Cellular senescence during aging and chronic liver diseases: mechanisms and therapeutic opportunities |
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155 | (24) |
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155 | (1) |
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Cellular senescence in the liver |
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156 | (2) |
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Mechanisms contributing to cellular senescence in liver |
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158 | (6) |
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158 | (2) |
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160 | (1) |
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Mitochondrial dysfunction |
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161 | (2) |
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163 | (1) |
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Therapies: senolytic and senostatic drugs |
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164 | (3) |
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165 | (1) |
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Senostatic/senomorphic drugs |
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166 | (1) |
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Conclusions and outstanding questions |
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167 | (1) |
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168 | (1) |
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168 | (11) |
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Chapter 7 Kidney diseases: fibrosis |
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179 | (26) |
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179 | (1) |
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Fibrosis is a common feature of unresolved kidney damage and kidney aging |
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180 | (1) |
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Glomerulosclerosis, vascular sclerosis, tubulointerstitial fibrosis |
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181 | (1) |
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ECM in renal homeostasis, injury, and repair |
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181 | (1) |
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Cellular senescence in renal aging, AKI, and CKD |
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182 | (1) |
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Different forms and different timing of cell-cycle arrest may have detrimental or beneficial effects in AM and CICD |
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183 | (2) |
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TIF and cellular senescence |
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185 | (3) |
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Senescence and the cellular origin of TIF |
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188 | (1) |
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Senescence-associated secretory phenotype |
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188 | (1) |
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Transforming growth factor-β (TGF-β) |
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189 | (1) |
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190 | (1) |
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The renin-angiotensin system (RAS) |
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191 | (1) |
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The antiaging factor Klotho |
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191 | (1) |
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Inflammation, innate immunity, and TIF |
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192 | (1) |
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Senescence and TIF-physiology and pathology |
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193 | (2) |
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195 | (10) |
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Chapter 8 Kidney diseases: transplantation |
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205 | (22) |
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205 | (1) |
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Factors determining donor organ quality and their association with senescence |
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206 | (4) |
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Impact of cellular senescence on transplant-related injuries and transplant outcome |
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210 | (2) |
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Rejuvenating and protecting kidney transplants |
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212 | (2) |
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214 | (13) |
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Chapter 9 Vascular diseases: atherosclerosis and atherosclerotic cardiovascular diseases |
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227 | (42) |
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Introduction-"a man is as old as his arteries" |
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227 | (1) |
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Features of cellular senescence in vascular cells |
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228 | (3) |
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228 | (2) |
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Vascular smooth muscle cells |
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230 | (1) |
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230 | (1) |
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Evidence of cellular senescence in atherosclerosis |
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231 | (4) |
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Evidence in human atherosclerosis |
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231 | (2) |
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Vascular senescence in mice models of atherosclerosis |
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233 | (2) |
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Factors involved in vascular senescence associated with the pathophysiology of atherosclerosis |
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235 | (8) |
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The renin-angiotensin-aldosterone system (RAAS) |
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235 | (1) |
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Sirtuins, NAD±, nicotinamide phosphoribosyltransferase (NAMPT) |
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236 | (2) |
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Hyperglycemia/diabetes and dyslipidemia (fatty acids, oxidized LDL) |
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238 | (1) |
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PI3K/Akt/mTOR, FOXO, AMPK, PPAR, PGC1a |
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239 | (2) |
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Noncoding RNAs (micro and long noncoding) in mediating vascular senescence |
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241 | (2) |
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243 | (1) |
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Therapeutics targeting cellular senescence for atherosclerosis |
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243 | (5) |
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Direct suppression of senescent signaling or modulating mediators driving cellular senescence |
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243 | (1) |
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Antisenescent effect of current therapies for atherosclerosis available in clinical settings |
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244 | (1) |
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Modulating metabolic signaling |
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245 | (1) |
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246 | (1) |
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246 | (2) |
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248 | (1) |
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Conclusions (limitations and perspectives) |
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248 | (1) |
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249 | (20) |
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Chapter 10 Diabetes: senescence in type 1 diabetes |
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269 | (20) |
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269 | (2) |
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The pathogenesis of type 1 diabetes |
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269 | (1) |
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Current clinical interventions for T1D and the role of beta cells |
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270 | (1) |
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Senescent beta cell accumulation as a novel pathogenic mechanism in T1D |
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271 | (7) |
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Molecular architecture of the beta cell senescence program in T1D |
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271 | (5) |
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Human beta cell senescence in T1D |
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276 | (1) |
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Roles of beta cell senescence in the pathogenesis of T1D |
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277 | (1) |
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Outstanding questions and future directions |
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278 | (3) |
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Mechanisms of senescent beta cell accumulation |
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278 | (1) |
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Senescence in other cell types in T1D |
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279 | (1) |
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Relationships between beta cell senescence and ER stress pathways |
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280 | (1) |
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Future clinical approaches to targeting beta cell senescence in T1D |
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280 | (1) |
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281 | (1) |
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282 | (7) |
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Chapter 11 Senescence in obesity: causes and consequences |
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289 | (20) |
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289 | (1) |
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Adipose tissue function in obesity |
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290 | (1) |
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Senescent cells accumulate in multiple tissues in obesity |
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291 | (2) |
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291 | (1) |
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291 | (1) |
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292 | (1) |
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292 | (1) |
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292 | (1) |
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293 | (1) |
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293 | (1) |
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Causes of cellular senescence in obesity |
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293 | (3) |
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293 | (1) |
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294 | (1) |
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294 | (1) |
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295 | (1) |
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295 | (1) |
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295 | (1) |
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295 | (1) |
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Threshold theory of senescent cell burden |
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296 | (1) |
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Implications of senescence in obesity: downstream effects |
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296 | (3) |
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296 | (1) |
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Inhibition of adipogenesis and ectopic lipid deposition |
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297 | (1) |
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NAD± depletion due to CD38± macrophage attraction |
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297 | (1) |
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Obesity-induced neurocognitive defects |
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297 | (1) |
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Paracrine effects on neighboring cells |
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298 | (1) |
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Promotion of cancer development |
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298 | (1) |
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Reduced regenerative potential |
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298 | (1) |
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Strategies to target obesity-related senescent cells |
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299 | (2) |
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299 | (1) |
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299 | (1) |
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SASP inhibitors or senomorphics |
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300 | (1) |
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Administration schedule of senescence-targeting therapies |
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300 | (1) |
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301 | (8) |
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Chapter 12 A framework for addressing senescent cell burden in the osteoarthritic knee: therapeutics, immune signaling, and the local-systemic interface |
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309 | (26) |
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310 | (1) |
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310 | (14) |
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Knee tissues degenerate in osteoarthritis |
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310 | (3) |
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Chronic presence of senescent cells in the knee accelerates osteoarthritic erosion |
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313 | (3) |
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Killing senescent cells in the knee can reduce OA-associated dysfunction |
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316 | (1) |
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Translating antisenescent therapies to the clinic for OA treatment |
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317 | (7) |
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324 | (1) |
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324 | (1) |
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325 | (1) |
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325 | (10) |
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Chapter 13 Osteoporosis and bone loss |
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335 | (28) |
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Osteoporosis as a public health problem |
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335 | (2) |
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The hallmarks of aging in bone |
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337 | (2) |
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The role of cellular senescence in mediating age-related bone loss |
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339 | (7) |
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Identification of senescent cells in the bone microenvironment |
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339 | (3) |
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Causal role for cellular senescence in mediating age-related bone loss |
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342 | (3) |
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Role of cellular senescence in mediating age-related frailty |
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345 | (1) |
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Estrogen deficiency and cellular senescence |
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346 | (2) |
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The role of cellular senescence in the effects of diabetes mellitus on bone |
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348 | (1) |
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Cellular senescence and radiation- and chemotherapy-induced bone loss |
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349 | (3) |
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Role of cellular senescence in the growth plate and regulation by parathyroid hormone-related peptide (PTHrP) |
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352 | (1) |
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353 | (1) |
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353 | (1) |
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353 | (10) |
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Chapter 14 Cellular senescence in neurodegenerative diseases |
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363 | (20) |
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Cellular senescence: driving force or beneficial response in neurodegeneration7 |
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364 | (2) |
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Postmitotic senescence in brain aging and neurodegenerative diseases |
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366 | (1) |
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Replicative senescence in brain aging and neurodegenerative diseases |
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367 | (1) |
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Demyelination, oligodendrocyte lineages, and Al plaque propagation in AD brains |
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368 | (3) |
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371 | (2) |
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Combination therapy for AD using senolytics and senomorphics |
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373 | (1) |
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374 | (1) |
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374 | (1) |
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375 | (6) |
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381 | (2) |
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Chapter 15 Cell senescence is a cause of frailty |
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383 | (42) |
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383 | (1) |
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How is frailty assessed in humans? |
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384 | (4) |
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How is frailty defined and assessed in experimental animals? |
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388 | (1) |
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What are the possible causes of frailty? |
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389 | (1) |
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390 | (3) |
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Does cell senescence cause frailty? How good is the evidence for it? |
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393 | (13) |
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Correlative evidence: associations between cell senescence and frailty |
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393 | (3) |
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Direct tests: reducing senescent cell burden |
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396 | (9) |
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Direct tests: enhancing senescent cell burden |
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405 | (1) |
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406 | (1) |
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406 | (2) |
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408 | (17) |
Part 3 Conclusions |
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Chapter 16 Senescence as a therapeutic target: current state and future challenges |
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425 | (18) |
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Jose Alberto Lopez-Dominguez |
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Biological interpretations of cellular senescence |
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425 | (3) |
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Senescence as the end point of cellular aging |
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426 | (1) |
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Senescence as a tumor suppressive mechanism |
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426 | (1) |
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Senescence as a general cellular response to damage |
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426 | (1) |
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Senescence as a cellular program involved in tissue remodeling |
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427 | (1) |
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Tissue remodeling by senescence is a two-step process |
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428 | (1) |
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The two steps of senescence in cancer |
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428 | (1) |
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The two steps of senescence in disease |
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429 | (1) |
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SASP-induced tissue repair versus SASP-induced tissue dysfunction |
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429 | (1) |
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Molecular triggers of senescence |
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430 | (1) |
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Triggers of senescence in vivo |
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431 | (1) |
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The challenge of detecting cellular senescence in clinical settings |
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432 | (1) |
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Potential side effects of eliminating senescent cells |
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433 | (1) |
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Senolytics as an anti-aging strategy |
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434 | (1) |
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435 | (1) |
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435 | (8) |
Index |
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