The Biology of Senescence 



differentiation, (2) when it has exhausted a particular store of 

 'growth energy', whatever the nature of such a store, or (3) 

 when it has carried out a certain stint of metabolism — a life- 

 span measurable in calories or in litres of oxygen consumed? 

 It is immediately evident that the programme in real organ- 

 isms is complex, that since senescence is a diverse process the 

 pacemaker differs in different forms. In some cases, when 

 ( 1 ) above has been satisfied, the further life-span of the differ- 

 entiated cells may depend upon their metabolism, as in (3). All 

 concepts based on 'wear and tear' in neurones or other cells 

 postulate a similar sequence: loss of regenerative power followed 

 by mechanical or chemical exhaustion. In the rotifer the normal 

 sequence of differentiation produces an organism which is 

 almost incapable of cellular repair, and quite incapable of 

 nuclear regeneration. The life-span of the adult, once this point 

 in the programme has been reached, is inversely proportional 

 to temperature and metabolic rate over a certain range. How 

 this effect operates we do not know. The encysted adult, 

 although unable to survive in the complete absence of oxygen 

 (Rahm, 1923) may pass years in diapause. The life-span of 

 many larvae can be enormously prolonged by underfeeding or 

 accelerated by heating: once metamorphosis has taken place 

 the programme is resumed but still responds to changes in tem- 

 perature by a change in pace. The longest-lived imagines, 

 termite queens, do in fact increase in size after eclosion (Harvey, 

 1934). In mammals it has been postulated that, since the meta- 

 bolic rate is held steady by various homoeostatic devices, the 

 essential ingredients of the programme leading to senescence 

 are growth and differentiation; that growth ceases as a result 

 of some process or processes of differentiation, and that the 

 absence of growth is a proximate cause of senescence. 



We have already suggested that this is not wholly in accord- 

 ance with the evidence. The observational test, that no verte- 

 brate which continues to grow undergoes 'morphogenetic' sen- 

 escence, and that all vertebrates which cease to grow are sub- 

 ject to it, does not appear to be satisfied, while the experimental 

 test, the demonstration that the life-span of an adult vertebrate 

 can be prolonged by keeping it artificially in continued growth, 

 beginning after normal size and development have been at- 



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