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DISCUSSION 



Danielli: I find it almost perplexing that the suggestion that the 

 plasticity of the cell — the relative absence of cross-linking — is funda- 

 mental to life, should be followed up by this observation of cross-linking 

 in ageing. This is so concrete a fact that it exposes in many ways the 

 bareness of the evidence for my hypothesis. Cross-linking could, as you 

 suggest, conceivably be a fundamental change, perhaps the most funda- 

 mental change at the molecular level. Collagen is, of course, an extra- 

 cellular system. Unfortunately, we know extraordinarily little about 

 the mechanisms of cross-linking in natural molecules. I wonder if 

 anyone feels able to make a comment on cross-linking mechanisms. 



Bourne: I do not want to comment on cross-linking mechanisms, but 

 in any collagen fibre there are various types of polysaccharide inside the 

 fibres and between the fibrils, and these must be taken into account in 

 any interpretation of age changes in collagen. I don't know to what 

 extent these play a part in this problem. 



Verzar: I was most impressed on hearing from Prof. Haddow* that 

 cross-linking may in some circumstances play a part in carcinogenesis. 

 For our own experimental results we have no other explanation to offer 

 than cross-linking. We do not know whether increase in cross-linking is 

 a general happening in the body. We also do not know why these cross- 

 linked molecules remain cross-linked and are not renewed. There are 

 some ingenious older hypotheses about cross-linking processes in ageing, 

 but at present we can only say that in certain cases we have really 

 proved that this happens. 



Comfort: It would be nice to know, Prof. Verzar, whether this occurs 

 in other animals, or in man, so that we could see whether there is any 

 relationship between the time scale of this change and the time scale 

 of the process of senescence. 



Verzar: We have tested this only on rats but it is possible that one 

 could start to work it out also for other animals. 



Comfort: The tendo Achillis in man should be fairly accessible. I 

 don't know how much surgical material you could get but you could 



* This referred to the possible role of cross-linking in the carcinogenic action 

 of certain of the biological alkylating agents, notably the nitrogen mustards ; 

 and to the question whether such carcinogenic agents merely expedite ageing 

 processes which occur spontaneously in their absence, and which may be 

 responsible for a proportion of so-called spontaneous tumours. — A. Haddow. 



