CONCEPT AND CRITERIA OF RADIOLOGIC AGEING 193 



with substantial doses for a long period of time, may involve the accumulation 

 of irreparable injury in a manner such that there would be increase in the 

 slope of a plot representing irreparable injury with passing time, as compared 

 with the simple persistence of a constant amount of irreparable injury 

 following a brief exposure (Fig. 2). However, under these conditions of expo- 

 sure, the injury picture is complicated by the constant production or existence 

 of mirej) aired injury of reparable types as long as irradiation is continued and 

 is probably different in animals irradiated until their death as compared with 

 animals whose irradiation is stopped far short of death. In either case the 

 unrepaired injury of reparable type may alter the susceptibility of the 

 animals to age-independent or age-dependent causes of death, the direction 

 and extent depending upon the dose-rate, changing tissue sensitivity, and the 

 balance between injury and recovery rates. 



If there is accumulation of irreparable injury with long protracted or 

 repeated irradiation it may be expected that such exposure may result in a 

 survival curve for experimental animals which is steeper in slope than the 

 control curve, i.e. a curve compatible with the concept of accelerated ageing 

 or increased incidence of age-independent causes of death or a combination of 

 the two. This is sometimes the case in protracted-exposure experiments. 

 However, in other instances the survival curves have been similar in shape to 

 the control curves, but simply advanced in time, compatible with the concept 

 of simple precocious ageing. This latter finding has led some investigators 

 (Neary et al., 1957) to the interpretation that at comparatively low daily 

 dose rates, shortening of life-span may be determinedmainly by the irradiation 

 received during the early part of the life-span. 



From these general considerations it can be seen that mortality data alone 

 are greatly limited as criteria of effect of total-body irradiation on the ageing 

 process. Such data are even more limited in their usefulness for this purpose 

 in the case of partial-body irradiation, caused for example by internally 

 administered radioactive isotopes. 



PATHOLOGY AND DISEASE INCIDENCE 



Survival curves coupled with data on the incidence and temporal distri- 

 bution of diseases and causes of death are more enlightening. However, in 

 order to bring such data to bear on the ageing process, there must be know- 

 ledge of the relative age-dependence of the causes of death, including recogni- 

 tion of the hereditary susceptibilities to causes of death which are more or less 

 age-dependent or age-independent. 



A well-kept ageing population of genetically heterogeneous animals tends 

 to die as a result of a relatively wide variety of age-dej^endent causes of death. 

 Many highly inbred, or genetically more homogeneous, ageing populations 



