278 PETER ALEXANDER AND MISS D. I. CONNELL 



is unmistakably due to the induction of two diseases, lung cancer and chronic 

 bronchitis, which are almost wholly absent in non-smokers. Yet radiation 

 has been claimed to accelerate the natural processes of senescence in small 

 mammals largely because it increases mortality rate for which, in general, 

 there is no obvious pathological explanation such as a great increase in 

 malignant disease (cf. Blair, 1956). 



The most compelling method for examining the hypothesis that radiation 

 ages is to compare the time-course of a number of physiological and bio- 

 chemical fimctions that vary with age in an irradiated and unirradiated popula- 

 tion. While there are a number of well-defined, quantitative tests for assessing 

 ageing in man (e.g. muscular power, sensory perception, skin elasticity, vital 

 capacity, memory) these cannot be satisfactorily applied to small mammals. 

 At present, only changes in the physico-chemical properties of collagen (see 

 Verzar, 1958) have been quantitatively related to age in rats and mice. 

 The force of contraction which collagen fibres develop on heating increases 

 regularly throughout life. Alexander and Connell (1960) showed that the tail 

 tendons of mice that had received 1,100 r of X-rays were indistinguishable 

 throughout life from those of unirradiated mice of the same age in spite of the 

 fact that the average life-span had been reduced by 40% by the irradiation. 



In the virtual absence of physiological tests comparative pathology 

 of irradiated animals can be useful. The hypothesis that radiation ages would 

 be supported if the onset of all diseases was advanced to the same extent and 

 by a factor comparable to that of the life-span shortening. Connell and 

 Alexander (1959) found that neither the time of appearance, nor incidence, of 

 benign hepatomas in CBA mice was influenced by 1,100 r. Yet in this strain 

 the incidence of this condition seems to be a function of age. 



Most other publications have been confined to the investigation of the 

 causes of death. If, under the conditions of the experiment, radiation is 

 powerfully leukaemogenic or carcinogenic, then an ageing effect will be 

 difficult to detect by post-mortem examination of animals that have died. 

 However, a number of workers, in particular Lindop and Rotblat (1961), 

 Furth et al. (1959), and Upton et al. (1960) have analysed the causes of death 

 in strains of mice where the carcinogenic action of radiation was not pre- 

 dominant. They found that the general pattern of the causes of death were 

 not altered by radiation, but that it was advanced in time and concluded that 

 radiation accelerated normal ageing processes. All these investigations suffer 

 from the serious drawback that post-mortem examination of animals that 

 have died of old age can provide reliable information for the cause of death in 

 only a fraction of the animals unless tumours or leulvaemia were involved. 



We have attempted to follow the onset and incidence of disease by killing 

 groups of ten mice at monthly intervals and subjecting them to a histo- 

 pathological examination of selected organs. We have confined ourselves to 



