The Biology of Senescence 



The concept of an expendable 'life ferment' appears to have 

 originated with Biitschli (1882), although he probably regarded 

 it simply as a material undergoing distribution from the germ 

 cells, where it is highly concentrated, to the somatic cells in 

 which it is increasingly diluted by subdivision. There are two 

 essentials for our acceptance today of a system in which sen- 

 escence depends on enzyme exhaustion in postmitotics — we 

 have to postulate (1) a fixed quantity of enzyme present in the 

 cell and exhaustible by use, and (2) the existence of an essential 

 enzyme replaceable only at cell division. The first proviso 

 appears already to be largely met, since it is known that the 

 effective life-span of enzyme molecules is finite in terms of mole- 

 cule-turnover (Mcllwain, 1946, 1949; Theorell et aL, 1951). 



The existence of enzyme systems renewed only at cell division 

 has not, it seems, been demonstrated as such, but with the 

 single general and large exception of 'hereditary materials', 

 nuclear and extranuclear, it has not been sought. Some direct 

 evidence might be derived from the action of known selective 

 blocking agents upon bacteria of protozoa. It will be evident, 

 however, that the idea of an 'enzyme replaced only by mitosis' 

 falls very close to some biochemical models of the gene, which 

 has been invested, either directly or at one remove, with direct 

 catalytic properties. Mcllwain (1946) has shown that in some 

 catalytic systems the number of enzyme molecules per cell is of 

 the order of unity. The inference from his figures is that if genes 

 are not themselves molecules acting as catalysts, each gene 

 during its 'lifetime' (i.e. between one cell division and the next) 

 produces one such molecule. Mcllwain (1949) also calculated 

 the life-span per molecule of the nicotinic acid co-enzyme com- 

 ponent of Lactobacillus arabinosus as representing the production 

 of 5-8 x 10 7 mol. lactic acid. Theorell (1951) in tracer experi- 

 ments demonstrated a very slow turnover of haemoprotein 

 enzymes, the exception being liver catalase which has a mole- 

 cule/life of only 4-5 days. The wastage of such systems is due, 

 presumably, in part to side reactions and non-specific inactiv- 

 ation, and in part to competitive inhibition or blocking by 

 metabolites partially resembling the correct substrate. If the 

 determination of such a single-molecule system were a cause of 

 cell senescence, and if the catalyst itself were to be identified 



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