296 A. C. UPTON, M. A. KASTENBAUM, AND J. W. CONKLIN 



ageing and therefore we are substituting something else. That is the real problem, as I see 

 it. Now to substitute death rate merely because we haven't got just the right experi- 

 mental conditions for ageing as yet, doesn't necessarily help. Tliis is not a criticism. It 

 may well be that a biochemical system or something of that sort may one day be dis- 

 covered and then we wUl, I'm quite sure, forget the problem of death in its variations and 

 go back to the real problem which is the effect of X-rays on ageing. 

 SCOTT: There is one point which I hope is fairly relevant to what we have been talking 

 about. It has been found that growing fish under adverse conditions shortened their 

 survival time, but that, by every other test of senility, such as the rate of tail regeneration 

 under adverse conditions the pace of ageing appeared to be reduced. 

 cottier: It may perhaps be useful to study a specific group of animals, namely the 

 oldest survivmg non-tumour-bearing animals that are killed in an apparently good 

 condition. Compare these animals with the oldest irradiated animals under the same 

 conditions. If you do that, you find that a number of things look very different with 

 these animals. For example, the degree of senescent atrophy of the liver is much higher 

 in natural senescence than in the oldest surviving irradiated animals. I have already 

 mentioned the difference in cartilage calcification. On the other hand the one thing, I 

 tliink it is almost the only thing, which was really visible in the irradiated animals that 

 lived longest was vascular change. I think that it will be worthwhile to learn more about 

 this change, to learn more about the generation time of epithelial cells, in order to 

 evaluate when they would be expected to reach the next mitosis, and so on. 

 casarett: I have another example of difficulties in this field. Take the heart for example. 

 The periodic examination of hearts, weigliing them and measuring fibres and so on, will 

 show that one gets in some animals decrease in heart weight and size and in other animals 

 increase in heart weight and size with advancing age. It appears that if you measure the 

 blood pressures of the animals you wUl find large hearts in animals that have hyperten- 

 sion, the small hearts are the true aged hearts uncomplicated by hypertension, and only 

 found in animals that do not have hypertension. In most of the animals that have 

 hypertension there is kidney disease. In serial sacrifice studies tliroughout life for the 

 study of the kidney, one sees, before symptoms are present, certain vascular connective 

 tissue changes, which until symptoms are present are not recognized by clinical patho- 

 logists or clinicians as representing a disease; nevertheless this is sub-clinical change. I 

 would like to emphasize again that one has to know the pathogenesis and mechanisms of 

 everything that is measured, and take into account the arbitrary lines dra\vn bj^ clinicians 

 as to what is a disease, and the gerontologist as to what is the change leading up to the 

 disease in order to make sense out of this compUcated process. 



mole: Surely you don't make measurements after you know the pathogenesis, j'ou make 

 the measurement in order to find out what it is. You said that you couldn't understand 

 what was wrong until you knew all about its pathogenesis and mechanisms, but what you 

 want to know is what the pathogenesis and mechanism is. 



CASARETT: I was interested in why some ageing rats have large hearts and some ageing 

 rats have small hearts at the same age, and I found out. There was a disease mvolved. 

 Before hypertension was recorded as a clinically recognizable disease of the kidney, there 

 were basic changes going on which, for the gerontologist, represent ageing changes, but 

 not all the animals wiU get clinically recognized nephrosclerosis and not all of the 

 animals will get hypertension, and therefore not all of the animals will get a large heart. 

 The distinction between what is a disease and what is a basic ageing change is what I 

 would Uke to make in this remark. In other words, a plea for gerontological science. 

 POCHiN: There is a bit of a separation coming here isn't there? Would you agree with this 

 first proposition that all deaths are due to some termmal change, caU it a disease if you 



