DIFFERENCES BETWEEN RADIATION-INDUCED LIFE- 

 SPAN SHORTENING IN MICE AND NORMAL AGEING AS 

 REVEALED BY SERIAL KILLING 



PETER ALEXANDER and Miss D. I. CONNELL 



Chester Beatiy Research Institute, Institute of Cancer Research, London, England 



SUMMARY 



Mice that had received m. several fractions a total dose of 1,100 r of X-rays were 

 kUled at monthly intervals and the liistopathology of selected organs exammed. The 

 results of the first two years of this investigation are reported. The onset of some diseases 

 and their incidence is quite unaffected by irradiation; for other diseases the latent period 

 is the same, but the incidence is higher in the irradiated group. In yet others radiation 

 advanced the time of appearance without altering the incidence. In addition whole- 

 body irradiation produces diseases that are not found m normal mice. These studies do 

 not support the view that radiation-induced shortening of life-span can be described as 

 an acceleration of normal ageing since tliis would require that the latent period of aU 

 diseases was advanced, but their incidence remains unaffected. It is concluded that other 

 experiments, in which the time-course of the various diseases was determined from post- 

 mortem examinations of mice that had been allowed to die, can be misleading and that 

 the method of serial killing is more rehable. 



The process of senescence is usually equated with the progressive impairment 

 of many, and diverse, physiological functions. A consequence of this physio- 

 logical deterioration is that the probability of an animal dying of certain 

 specific diseases increases. The end effect of senescence is to impose an upper 

 limit on expectation of life and in this sense death and ageing are related. We 

 do not thmk that it is useful to consider ageing as a direct cause of death. The 

 force of mortality, though related, is not a measure of senescence. A number 

 of authors have referred to any process which shortens life-expectancy (i.e. 

 one which shortens the time axis but not the over-aU shape of a typical sur- 

 vival curve of an accident-free population) as an acceleration in ageing. Such 

 an approach leads to obvious absurdities. For example, any carcinogenic 

 stimulus with a long latent period wiU produce this effect, yet in reality the 

 treatment produces a new disease and need in no way be an acceleration of a 

 normal process. The effect of heavy cigarette smoking — started in adole- 

 scence — causes a shortening, by some 15%, of the time needed for 50% of the 

 population to die — the average life-span — but apart from this contraction 

 of the time axis the shape of the survival curve of smokers and non-smokers 

 is very similar (R. A. M. Case, private communication). In man, smoking is 

 not said to accelerate senescence because the change in the mortality curve 



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