PMID: 7334944Dec 1, 1981Paper

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

Medical Hypotheses
E Jablonka, P Jablonka

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, than 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.

References

Jan 1, 1977·Annual Review of Genetics·S Wolff
Sep 1, 1979·Mutation Research·J K WienckeH Paulus
Nov 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·R S ChagantiJ German
Jun 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·R W Hart, R B Setlow
Mar 1, 1965·Experimental Cell Research·L HAYFLICK
Nov 1, 1956·Proceedings of the National Academy of Sciences of the United States of America·N E MortonH J Muller
Jan 1, 1959·Proceedings of the National Academy of Sciences of the United States of America·L Szilard

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Citations

Nov 1, 1987·Mechanisms of Ageing and Development·C B Olson
Aug 1, 1983·Biological Reviews of the Cambridge Philosophical Society·S C Makrides
Dec 7, 1982·Journal of Theoretical Biology·P Jablonka, E Jablonka

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