General Discussion 139 



achieved the last tunc and try to improve on it. It may just as likely be 

 a psychological test as a physical one. 



Freeman: That is true. As a matter of fact these people didn't know 

 what their particular endurance was. 



Parkes: Dr. Rubin, if you had a sample of urine given you, could you 

 tell with certainty wiiether it came from an old or a young man, or an 

 old or young woman? 



Rubin: Not with certainty, because as I pointed out there was this one 

 man of fifty-two who had a level which w as twice that of the mean of 

 the young men. But I was very much surprised at his result. The 

 young ones range from a total of 5-6 mg. to 18 or 20, whereas the older 

 people will range from 1 • 9 to 5, if that. There is occasionally an overlap. 

 But the values in our charts show standard error, not standard deviation, 

 and there is a significant difference between old and young people on 

 that basis. 



Parkes: But not between male and female? 



Rubin: No. 



Krohn: Miss Rubin, about the precursor of all these hormones: you 

 say it can be either cholesterol or acetate. These two substances seem to 

 be so different chemically that I do not see how you imagine any 

 particular enzyme system coping with both of them. 



Rubin: I was very careful to hedge about that. Dr. Hechter and his 

 group are at present engaged on perfusing adrenals with various 

 precursor substances, but the whole thing is very much in a state of 

 flux. I can only say that the major block seems to be in the production 

 of dehydroepiandrosterone. 



Krohn: Have you any information about the response of these old 

 people to ACTH? Are they perhaps leading a less exhausting and 

 stressful life, and would they respond to a standard dose of ACTH in 

 exactly the same way as the younger people? 



Rubin: We did some work several years ago when we gave 25 mg. 

 ACTH a day to various age groups, and we couldn't show any difference 

 either in total excretion or in individual patterns. We couldn't demon- 

 strate any great response to the dose of ACTH at any age. It may be 

 that it should have been given by continuous intravenous infusion. 



Shock: We carried out studies on this subject in our laboratory some 

 years ago, both in terms of response to a single dose of ACTH* and also 

 the metabolic responses to continued administration over a period of 

 six weeks t. We observed our subjects on a metabolic balance regime 

 throughout the entire period. Balances for nitrogen, Ca, P, Na, K etc., 

 were all followed. Although we found individual differences in responsive- 

 ness to the continued administration of ACTH, they were not related to 

 the age of the subject. We w'cre very disappointed. 



Medawar: Why do you call that a disappointing result? It seems to 

 me an intensely interesting one, of perhaps fundamental character. 



Shock: Well, it was disappointing because at that time, which was 

 * Solomon, D. H. and Shock, N. W. (1950) ./. Geront., 5, 203. 

 t Duncan, L. E., Solomon, D. H., Rosenberg, E. F., Nichols, M. P. and 

 Shock, N. W. (1952) J. Germit., 7, 351. 



