The Study of the Ageing of Cells 43 



The primary nature of deleterious changes 



When a change in cell behaviour with age is observed such as 

 the change in daughter cell fate noted above, it is desirable to 

 trace the change to a primary source. Among the factors to 

 be examined are: 



(a) mutations in chromosome major genes, polygenes, 

 plasmagenes and homeostats; 



(b) infection with viruses, etc. ; 



(c) accumulation of toxic products of metabolism. 



Unfortunately most of the techniques which are necessary 

 for examining these factors in somatic cells remain to be 

 worked out. We may note that we do not know whether 

 mutation of a single major gene in a tissue cell will result in 

 cell death. It may be that the resultant deficiency can be 

 made good by neighbouring cells. But the accumulation of 

 many such mutations in the cells of an organ must limit the 

 overall resilience and competence of the organ. Those cellular 

 characteristics which are controlled by polygenes, i.e. inherit- 

 ance of which is quantitatively continuous and not controlled 

 stepwise by one or two major genes, would appear to be 

 particularly likely to be involved in senescence, since mutation 

 of several genes in a polygene set would not result in death of 

 the cell, but in a quantitative diminution of the efficiency 

 with which the appropriate cell activity can be performed. 



Since the differences between somatic cell lineages appear 

 to reside in their cytoplasms, we may also expect reduction in 

 cellular competence to be caused by mutations of plasmagenes 

 and homeostats.* The distinction between a deleterious 

 nuclear change and a deleterious cytoplasmic change can 

 probably be established by nuclear transfer, but the more 

 detailed analysis of primary changes needs much more 

 attention. 



* A homeostat = an organization of macromolecules or of processes which 

 is self-reproducing, and which normally carries out or controls at least one 

 cellular function, e.g. chloroplasts, kinetosomes (Danielli, 1956. Nature, Lond., 

 178, 214). 



