The Mechanisms of Senescence 



with the gene, we would evidently need to postulate a copying 

 mechanism at mitosis in which inactivation of the catalytic 

 portion of the system (1) does not interfere with the production 

 of a copy, and (2) is itself reversible : or, alternatively, one in 

 which the products of division are two copies, not an original 

 and a copy. It can, of course, be argued that when a differ- 

 entiated cell in fact undergoes senescence, we cannot infer 

 whether any system in it would be renewed by further division. 

 Its failure to divide, even if that failure is a physiological one, 

 leading to final differentiation, may be due to the loss of a 

 copying mechanism. This type of problem has been encountered 

 already, however, by workers attempting to explain some of the 

 results of research on adaptive variation in Neurospora and 

 yeasts. 'Unless gene reproduction and gene action are totally 

 independent of each other, we have to reconcile the uniformity 

 in the reproduction of genes with the enormous variation in what 

 we believe to be their primary products' (Pontecorvo, 1946). 

 Classical genetics, although they allocate an equal proportion 

 of nuclear genie material to every cell, have so far given little 

 direct information about the activity of this material in cells of 

 different kinds at any time except during mitosis, and a new 

 category of study ('epigenetics') has had to be coined to cover 

 this activity. Of the large number of subsidiary copying pro- 

 cesses which have been inferred from adaptation experiments 

 and work on anuclear portions of cells some apparently con- 

 tinue undiminished throughout the intermitotic period. The 

 power of adaptive enzyme production persists in yeasts rendered 

 non- viable by X-rays (Spiegelman, Baron and Quastler, 1951). 

 In a neurone which may remain functioning in man for over 

 a century, either the enzymic mechanism which maintains cell 

 metabolism is continuously kept in repair, or it is of a kind 

 which is almost invulnerable to incidental spoilage by use. The 

 survival-time of non-dividing cells varies greatly, even between 

 closely related organisms: thus in Rotifers, the life-span reaches 

 5 months in Callidina (Zelinka, 1891) and even, perhaps, several 

 years in certain bdelloids (Murray, 1910). If 'wear' is to be 

 invoked in these cases where senescence occurs in the presence 

 of cellular determinancy, then the susceptibility to it must vary 

 enormously. Other cells — squamous epithelium, for example — 



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