title: Individual Cell Longevity, 'Life's Timekeeper', and Metazoan Evolution.
abstract: It is proposed that a primary and fundamental aspect of metazoan evolution is an ability to control and extend the longevity of individual cells. This was achieved through an intracellular oscillator, dubbed 'Life's Timekeeper', which evolved in the hypothetical ancestor of all metazoans. Slower oscillatory frequencies directed metazoan evolution towards extended longevity of individual cells, enabling generation of many specialised types of terminally differentiated cells. As the longevity of these cells was still relatively short in more primitive metazoans, stem cells, capable of differentiating into all specialised cell types, were retained in order to replace senescent cells. With increasing cell longevity, continual replacement of all senescent cells was no longer necessary. Cells such as neurons could be sustained throughout life, enabling the evolution of brains, hence, complex behaviour and intelligence. In multicellular metazoans the oscillator remains synchronised across all cells. It coordinates the timing of all cell-cell signalling systems, hence controls the timing of development and aging/senescence. In advanced metazoans, where senescent cells are not continually replaced, it controls lifespan. With regards to morphological evolution the oscillator, through alterations to developmental timing, controls change in size and shape. With regards to life history theory it functions as the key variable mediating the correlation between life history traits. This theory is compatible with a prominent role for environmental selection but, as it implicates some degree of internal mediation and direction, it is not entirely compatible with the 'modern synthesis' view of natural selection.
authors.affiliation: University of Newcastle, Wear Base Unit, Monkwearmouth Hospital, Newcastle Road, Sunderland SR5 1NB, UK. david.neill@ncl.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Neill
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002470:Cell Survival; D016922:Cellular Senescence; D006801:Humans; D015398:Signal Transduction