440 SENESCENCE AND REJUVENESCENCE 



in the relative volume of the cytoplasm rather than of the nucleus. 

 Hertwig assumes that the cell is able to regulate its own nucleo- 

 plasmic relation, at least within certain limits, but the origin and 

 nature of the nucleoplasmic tension which he postulates as the 

 basis of this regulation, as well as the physiological mechanism of 

 regulation, remain obscure. In short, the hypothesis has not a 

 physiological foundation and apparently is not in complete agree- 

 ment with the facts. 



Minot's views, which are fully stated in his recent publications 

 (Minot, '08, '13), are almost diametrically opposed to those of 

 Hertwig, as regards the direction of change in the nucleoplasmic 

 relation during senescence. Minot attempts to show that the 

 growth and differentiation of the cytoplasm are the fundamental 

 factors in senescence and death. In the young cell the amount of 

 cytoplasm in relation to the amount of nuclear substance is least, 

 but during development it increases and undergoes differentiation, 

 " cy tomorphosis ' occurs, and brings about senescence. 



According to Minot this is a universal law, but his evidence is 

 taken almost entirely from the higher animals. In many of the 

 lower animals no marked proportional increase in the amount of 

 cytoplasm occurs during development, and in the plants differ- 

 entiation is in genera] accompanied, not by increase in the cyto- 

 plasm, but by vacuolization. Therefore the size relations of the 

 cytoplasm and nucleus, while they may serve to some extent as an 

 index of age in the higher animals, cannot by any means be regarded 

 as a universal factor in senescence. But the differentiation of the 

 cytoplasm undoubtedly is a very important factor in senescence, 

 and as regards this point my own view ag^es closely with Minot's. 



The changes in the substratum of the cells are merely the con- 

 ditions or one aspect of senescence, they are not senescence itself, 

 for that is a change in the dynamic processes of the organism which 

 ends in their cessation. Minot, however, has not told us what 

 senescence is nor how the cytoplasmic changes bring it about. I 

 have attempted to show that senescence is a decrease and rejuve- 

 nescence an increase in rate of metabolism associated with changes 

 in the cellular substratum which themselves result from the relation 

 between substratum and metabolism (Child, 'n, '14). In his 



