The senescence of postmitotic mammalian cells: a cell-clock hypothesis.
A cell-clock hypothesis for the senescence of long-lived postmitotic cells is proposed, based on the concept that the cells cycle regularly between a synthetic and a degradative phase and that the synthetic phase of each cycle is initiated by transcription of a family or families of highly repetitive DNA. The initiator transcripts are conceived to activate other segments of DNA controlling the transcription of mRNAs. The basic senescence mechanism is postulated to be the uncorrected progressive conversion of 5-methylcytosine in repetitive DNA to thymine by hydrolytic deamination, causing an age-related decline in the number of active initiator transcripts and a progressive loss of cell vigor.
D044503:5-Methylcytosine; D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000235:genetics; D008168:Lung; D008938:Mitosis; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D012333:RNA, Messenger; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA