ZEE-FEN CHANG2021-05-312021-05-3119970929-6646https://www.scopus.com/inward/record.uri?eid=2-s2.0-0030827525&partnerID=40&md5=0fc0e892041b024d3bd35d6b1eb2b979https://scholars.lib.ntu.edu.tw/handle/123456789/564394Normal human diploid fibroblasts cannot divide indefinitely in culture. At the end of their lifespan they withdraw from the cell cycle permanently by a process termed cellular senescence. Recent molecular studies indicate that upregulation of two inhibitors of cyclin-dependent kinases, p16 and p21, is responsible for blocking the G1/S transition in senescent cells. Although the state of senescence resembles terminal differentiation in that both exhibit irreversible growth arrest and resistance to apoptosis, other molecular changes are seen only in senescent cells. This suggests that the signal pathway specific for senescence is present in normal cells. Changes in chromosomes, such as progressive shortening of the telomeres and erosive damage by detrimental by-products in metabolism, may he the signals that trigger senescence, leading to the inactivation of cell cycle progression. On the other hand, it seems that a dominant genetic program is intrinsically preset to ensure a growth limit in the normal cell. This notion is supported by cell fusion and microcell transfer experiments which show that escaping from senescence requires recessive mutations in senescence-specific genes. Identification of these participating genes and clarification of their mode of action will provide the basis for understanding the mechanisms governing the differences between mortality in normal cells and immortality in cancer cells.Apoptosis; Cell cycle; Cyclin-dependent kinase inhibitor; Senescence; Telomere[SDGs]SDG3cyclin dependent kinase; apoptosis; cell aging; cell cycle; etiology; fibroblast; human; human cell; lifespan; regulatory mechanism; review; senescence; telomere; Animals; Apoptosis; Cell Aging; Cell Division; Chromosome Aberrations; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; G1 Phase; Humansreview93439772-s2.0-0030827525