/ 



282 PETER ALEXANDER AND MISS D. I. CONNELL 



deaths in both control and irradiated animals are probably due to renal failure 

 in the last stages of papillonephritis. As, however, the life-expectancy of the 

 treated mice is much less than for the unirradiated, the fraction of animals 

 developing this kidney lesion from 18 months of age rises much more rapidly 

 amongst the irradiated than amongst the controls. There is, however, no 

 indication that the latent period of this disease is altered by radiation. 



Though this study using serial killing is as yet incomplete, the results that 

 have been obtained so far are not consistent with the hypothesis that radia- 

 tion advances all diseases. The effect of radiation on late somatic changes 

 is extremely complex and most conceivable variants were seen in this in- 

 vestigation. 



(1) The time-course and incidence are completely unaifected by 1,100 r in 

 spite of the fact that the disease seems to be related to age (i.e. like the ageing 

 changes in coUagen). 



(2) The latent period is unaffected but the incidence is increased. 



(3) The latent period is shortened but the total incidence is increased. 



(4) The latent period is shortened but the total incidence remains imaltered. 



If radiation were to induce a process akin to normal ageing then most of 

 the major pathologies should fall into the last category. There is yet another 

 possible variant, namely that radiation delays or prevents certain diseases. 

 An example has not been observed by us but has been seen in strains of mice 

 having a high leukaemia incidence. 



None the less an understanding of the biochemical mechanisms that lead 

 to radiation life-span shortening may materially advance knowledge about 

 some of the processes responsible for agemg. It seems unlikely that there is 

 one basis effect at either the chemical or cellular level which is responsible 

 for the physiological changes which in toto are changes known as senescence. 

 The relative contributions of the different processes may be different in 

 different animals. Radiation may imitate one or more of the biochemical 

 reactions that lead to ageing, bub it does not reproduce the whole complex. 

 Before the aetiology of ageing can be understood at the sub-ceUular level it 

 must be broken down into a number of different biochemical pathways each 

 of which causes an upper limit to appear in the life-span of an animal. Radio- 

 biology may pin-point some of these life-limiting factors. 



This investigation was supported by grants to the Chester Beatty 

 Research Institute (Institute of Cancer Research: Royal Cancer Hospital) 

 from the Medical Research Council, the British Empire Cancer Campaign, the 

 Anna Fuller Fund, and the National Cancer Institute of the National Insti- 

 tutes of Health, U.S. Public Health Service. 



