194 G. W. CASARETT 



of animals tend to show a lesser variety of causes of death and usually a high 

 incidence of certain specific causes of death for which they have a strong 

 genetic susceptibility. In general, the age-dependent diseases or the so-called 

 diseases of ageing are essentially either degenerative or neoplastic in character, 

 and it is well-known that many of the neoplastic diseases develop in relation 

 to previously developing degenerative tissue states either at the site of origin 

 of the neoplasms or in some physiologically related tissue. 



As in the case of ageing manifestations, the propensity for development 

 of diseases is not uniform with respect to individuals of a population or organs 

 of an individual. Some diseases are more or less progressively age-dependent. 

 Other age-dependent diseases show considerable age-specific propensity, the 

 incidence rismg rapidly to a peak at certain ages and then declining rapidly 

 after those individuals with a genetic tendency for the disease have died. 



In order to establish a baseline for interpretation of the ageuig process by 

 means of data on disease incidence or cause of death, it is necessary to know 

 the age-dependent diseases in a well-kept ageing population, and to also 

 recognize the possibility that diseases or causes of death which are relatively 

 age-independent, whether they be infectious diseases or degenerative or 

 neoplastic diseases, for which there is very strong genetic propensity, may be 

 extraordinarily increased in incidence or time of onset by relatively little 

 tissue injury, and be relatively independent of change in the ageing process. It 

 is necessary to recognize that increased or decreased mcidence of age- 

 independent causes of death may change, in relative fashion, the age- 

 specific incidence of age-dependent diseases expected in an undisturbed 

 control population. Furthermore, for a better understanding of the disease 

 picture in relation to the ageing process, it is necessary to be able to distin- 

 guish between temporal advancement of disease and true induction of disease. 



If an agent results in the earlier appearance of a disease in a population, 

 with increase in age-specific incidence at earlier ages and without a signi- 

 ficant increase in absolute or life-time incidence, as compared with controls 

 in a well-kept ageing population, then the disease may be regarded as having 

 been temporally advanced by the agent. When the agent results in a con- 

 siderable increase in absolute incidence of a disease as compared with the 

 incidence expected within the maximal life-span of the species or strain, then 

 the excess incidence of the diseases may be regarded as having been induced 

 by the agent. 



It is well-known, however, that the observed mean life-spans of experi- 

 mental animal populations often fall far short of their potential averages 

 because infectious diseases kill, or damage, large numbers of individuals well 

 before the senescent period of life. Some age-dependent diseases of long 

 latency may rarely, or never, develop spontaneously within the observed life- 

 span in many individual experiments. Consequently, it is possible m some 



