44 J. F. Danielli 



The causes of primary changes 



Where the primary change is an infection, or an accumula- 

 tion of toxic products of metabolism, the cause may need 

 little further elucidation. But where the primary change is in 

 one of the cellular control mechanisms the establishment of 

 the nature of the primary defect may throw little light on the 

 causal agent. Where mutation has occurred it may be due to 

 radiations, to mutagenic chemicals or to faulty replication. 

 Changes in homeostats — resulting for example in a change in 

 antigenic type — may be the result of an endogenous process, 

 or result from exogenous agents such as infections, exposure to 

 foreign macromolecules, or to promoting agents. So far as the 

 study of senescence is concerned we are still almost completely 

 in the stage of establishing changes in function with age, so 

 that the establishment of the nature of primary causal agents 

 is at present almost an academic point. Insofar as we are 

 successful in carrying through the programme outlined, it 

 will become less academic. 



Conclusion 



The final step in the study of cellular ageing will be to find 

 means either of preventing or reversing the primary changes. 

 One point which must be emphasized is that, even when all 

 other sources of ageing have been removed, somatic mutation 

 will remain. Thus if there is ever to be a complete control of 

 senescence we shall need to be able to prevent, or to reverse, 

 somatic mutation. 



DISCUSSION 



Bald: Our data on pathology in ageing cells are comparatively few, 

 and one of these is the accumulation in ageing cells of some pigment 

 substances. This is particularly well known in nerve cells ; we find that 

 in old age, intervertebral ganglionic cells, especially, are full of pigment 

 granules, both in animals and in man. 



Prof. Danielli spoke of changes in the function of the cells. I should 

 like to contribute that in ageing cells one can find very marked changes 

 in hormone or enzyme production. I have studied the pancreas of young 

 and old animals and even of humans and found that enzyme production 



