Genetic and molecular basis for cellular senescence.
Normal human and rodent cells in culture exhibit a finite life span at the end of which they exhibit morphological changes and cease proliferating, a process termed cellular senescence or cellular aging. Many cancer cells differ from normal cells in that they do not senesce and have an indefinite life span in culture, suggesting that alterations relating to cellular senescence are involved in the neoplastic evolution of tumor cells. Recent experimental results strongly support a genetic basis for cellular senescence. Defects in the senescence program in transformed cells can be corrected by introduction of a specific chromosome from normal cells into the abnormal cells. Using this approach, possible senescence genes have been mapped to specific chromosomes. Cell cycle control genes that regulate entry into the DNA synthetic phase of the cell cycle must be altered in senescent cells. Recent findings suggest that phosphorylation of the retinoblastoma gene is altered in senescent cells. It is possible, but not yet proven, that aging at the cellular level contributes to the aging of the individual. Therefore, an understanding of cellular senescence at the genetic and molecular levels may provide new insights into both the cancer and aging processes.
Barrett
J C
JC
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Annab
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LA
Futreal
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D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002459:Cell Fusion; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D006224:Cricetinae; D003412:Cricetulus / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology; D016161:Genes, Retinoblastoma; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology*; D007399:Interphase; D008136:Longevity; D008168:Lung / Q000166:cytology; D008647:Mesocricetus / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics; D012377:Rodentia / Q000502:physiology; D013045:Species Specificity
D005819:Genetic Markers; D016160:Retinoblastoma Protein; D016203:CDC2 Protein Kinase