The Biology of Senescence 



have a function which depends on the progressive change in their 

 structure and metabolism from formation to complete cornifi- 

 cation. This implies a process of chemical heterauxesis within 

 the cell, and all such 'open-ended' systems, if they continue, 

 must eventually destroy homoeostasis. The development of 

 histochemical methods of detecting enzymes in cells, and of 

 selective blocking agents which irreversibly inactivate particular 

 enzymes, already suggest experiments by which we might learn 

 something of the limits of the postmitotic cell's power to re- 

 generate its enzymic complement, and detect long-term changes 

 in this power. 



A special case of limited survival in the non-dividing cell is 

 provided by the mammalian erythrocyte. This is one of the few 

 cell-types for which a life-table can be constructed. The form 

 of the curves obtained by a variety of methods indicates that 

 the decay of circulating erythrocytes is a true 'senescence', i.e. 

 that the probability of the destruction of a given cell increases 

 markedly after it reaches a certain age. There is also, apparently, 

 an 'infant mortality' among newly-formed red cells to make the 

 mimicry of a metazoan survival curve even closer. 



The cause of erythrocyte 'senescence' has been the subject of 

 a good deal of study. Although it is probable that the proximate 

 cause of erythrocyte destruction is a change in the physical 

 properties of the stroma or the envelope of the cell, there is 

 considerable evidence that the timing mechanism in this in- 

 stance is the deleterious effect on other intracellular systems of 

 the products of one particular oxidation-reduction system, in 

 which methaemoglobin is formed from haemoglobin. The evi- 

 dence for this view has been reviewed by Lemberg and Legge 

 (1949). In this case we are dealing with a specialized, anuclear 

 cell — in the nucleated avian erythrocyte, haemoglobin syn- 

 thesis, and possibly other processes of renewal, continue in the 

 circulation, but the life-span is, curiously enough, very much 

 shorter (Hevesy and Ottesen, 1945; Hevesy, 1947) than that of 

 the mammalian red cell. 



6-1-2 CELL TURNOVER 



It is necessary to point to a widespread impression among 

 medical writers on senescence that cell turnover in the organs 



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