Discussion 45 



decreases with age. Recently, Dr. Banga and I found that elastase pro- 

 duction ceases in old age, so that in old age possibly there is no elastase 

 in the pancreas. Prof. Danielli, have you had any similar findings in 

 ageing cells in protozoa or in lower animals ? 



Danielli: It is quite true there are phenomena, in protozoa for example, 

 which might be regarded as analogous, but I think the more important 

 thing is that strictly speaking your observations are not an examination 

 of cells in themselves but an observation on cells in a complicated 

 organism, taken out and studied at different times during the life cycle. 

 Now, that means that what you have seen may be due to a direct 

 ageing of the cells, or may be due to some ageing process at a much more 

 complicated level. My communication dealt exclusively with what would 

 go on within a cell as a result of its own constitution and inevitable 

 interactions with the inorganic environmental factors, and not things 

 which might occur as a result of relationships between cells. So I would 

 think that, whereas looked at from the point of view of whole-animal 

 studies, those are very interesting investigations which you have made, 

 yet looked at from the point of view of cellular studies they are not so 

 interesting because one does not really know what it is that is affecting 

 the cell, whether it is something which is intrinsic to the cell itself, or 

 whether it is something that is intrinsic to an organ or to a whole animal. 

 My reason for limiting very sharply my communication to the cellular 

 level is that I think that one of the things we have got to do, in the study 

 of ageing, is separate out those things which are fundamental to the 

 extracellular level from those which are fundamental to the multicellular 

 level. 



Friedman: Prof. Danielli, I respect heartily the manner in which you 

 have circumscribed the limits of the field that you have been discussing, 

 but I wonder, when dealing with the problem of ageing and the ageing 

 of cells, whether we really can so sharply isolate the cell from its environ- 

 ment? Can we, for instance, speak of the ageing of the cell without 

 speaking of the ageing of its environment ? If one studies, as we have 

 done, sodium transport systems in smooth muscle in vitro, one can get 

 entirely different results depending on the medium one uses and, indeed, 

 on whether one uses fresh plasma or old plasma or fresh serum or old 

 serum. Now, there the environment has, in a sense, aged; can one separate 

 off the ageing of the environment from the ageing of the cell even though 

 I admit that, ideally speaking, one would like to ? 



Danielli: I think one has got to if one is going to understand the 

 details of any process of ageing. To begin with, in any separate cell the 

 overall genetic constitution may be such that that cell has a limited life 

 irrespective of anything that may be environmental. Secondly, it is 

 quite inevitable that there will be mutagenic factors acting upon that 

 cell — radiations, mutagenic chemicals, and so forth — which are in only 

 a very special sense an environmental factor and which set an ultimate 

 life to that cell; obviously, somatic mutation will ultimately cause every 

 cell to die which does not first die from other causes. We have to sepa- 

 rate out these factors and assess them separately from those things which 

 come in as a result of interactions with the environment. It is not that 



