A model of senescence as the piecewise loss of control over transcription

Abstract

Given that the transcription of DNA into heterogeneous nuclear RNA (hnRNA) is controlled for each species of hnRNA by an on-off switch at the beginning of each hnRNA template, then control over transcription may be independently lost over each control site. If an incorrect switch setting is conserved during replication and mitosis after the pattern of conservation of DNA-binding molecules and DNA bound histones, then the errors are heritable and can accumulate from one cell generation to the next. This type of control system failure is hypothesized to be the basis of senescence. This theory easily explains the Hayflick limit for cultured cells, the link between ageing and cancer and the reason why haploid animals are much rarer than haploid plants. This theory predicts that a haploid animal will accumulate senescence at over 100 times the normal rate, and therefore that obtaining a haploid animal will be virtually impossible. The implications for the control of senescence and possible strategies for preventing or repairing switch mis-settings are discussed.