48 Discussion 



dealing then with an older skeleton when, in fact, you have got one 

 with completely new molecules ? 



Danielli: I don't regard the composition, shall we say the newness, 

 of any particular atom in a particular macromolecule as being import- 

 ant; what I do regard as being important are the processes which con- 

 trol which atoms shall be present in which places, and it is at these control 

 processes that you have to look for some of the fundamental changes 

 which occur in ageing. 



Gillman: I realize that my remarks that follow are not on the cellular 

 level; nevertheless, there is some evidence that the view which Schoen- 

 heimer and his collaborators put forward concerning the speed of inter- 

 change of molecules in certain tissues (such as bone, mentioned by Dr. 

 Bourne) does not seem to hold to the same extent in certain other 

 apparently important connective tissues. According to recent studies, 

 the rate of turnover of molecules in structures like collagen is relatively 

 slow. In fact, I was rather surprised to learn that it is believed that 

 collagen fibres, once laid down, e.g. in a more or less mature rat, would 

 stay in the animal to the end of its life. However, Dr. J. Gross has recently 

 indicated that even an extract of collagen fibres actually ages, even at 

 about 2° or 3° C — ageing here being judged by the solubility and other 

 characters of the extract. I don't know how far decrease in speed of 

 turnover is related to ageing, or, as Prof. Danielli has mentioned, how 

 far ageing affects the kind of molecules which move in and out of a 

 particular organized structure. I mention this possibility because there 

 are certain kinds of structural proteins within cells and even within 

 extracellular fibres which may perhaps decrease their speed of molecular 

 turnover with ageing more than others. 



Danielli: Yes, that is absolutely certain; deoxypentose nucleic acid 

 scarcely turns over at all and it is, in a sense, one of the most important 

 control elements. 



Gillman: Are there any others that you know of? 



Danielli: American workers on adaptive enzymes have been able to 

 show that in some circumstances the turnover of an adaptive enzyme 

 is extremely small compared with the rate of synthesis of adaptive 

 enzyme in the presence of the activating substrate. But Schoenheimer's 

 experiments make it quite clear that many other proteins are subject 

 to rapid turnover. 



Gillman: Prof. Danielli, you made a remark a moment ago which I 

 would like to question if only to get clarity on this point. You said that 

 certain structures in the cell were the more stable in that they did not 

 change so rapidly in the cell, and you apparently went further and im- 

 plied that the stability of a molecule within a cell gave that molecule 

 a particular regulating function within the cell. 



Danielli: No, I did not wish to convey that at all. One thing that I did 

 want to emphasize, however, is that the fact that deoxypentose nucleic 

 acid does not interchange its parts very often does very likely give it 

 a special stability which it would not otherwise possess. Every time a 

 nucleotide or an amino acid is moved in and out of a macromolecule, 

 a possibility of error comes in, when carrying out the synthesis. So that 



