TEE SIZE OF ORGANISMS i95 



with a small amount of such protoplasm, while large nuclei occur only 

 in cells with a large amount. It is not the increase in the general pro- 

 toplasm which causes the nuclei to become relatively small, but rather 

 the increase in the differentiation products and the corresponding de- 

 crease in the general protoplasm. 



In most respects I am in hearty accord with Minot's latest formula- 

 tion of the causes of senescence.^^ In this work he particularly empha- 

 sizes the effect of differentiation in causing senescence. Indeed he con- 

 cludes, "dass die Diffei^enzierung als die wesentliche TJrsache des Alt- 

 werdens zu betrachten ist." Nevertheless, he still holds that the greater 

 growth of the protoplasm, relative to the nucleus, is the essential basis 

 of differentiation; and that we may distinguish in development an 

 earlier and shorter period, which is characterized by the preponderating 

 growth of the nucleus, from a second and longer one characterized by 

 growth and differentiation of the protoplasm — the former being the 

 period of rejuvenescence, the latter the period of senescence. In 

 Crepidula, as I have shown,^* the growth of nuclear material during 

 early cleavage is not greater than that of the protoplasm, and in general 

 the size of a nucleus is directly proportional to the quantity of general 

 protoplasm and to the length of the resting period, because general 

 protoplasm is absorbed by the nucleus during interkinesis, whereas 

 products of differentiation do not enter the nucleus. A causal explana- 

 tion is thus given of the relation between nuclear size and cell size at 

 different stages of development; and in the fact that differentiation 

 products can not enter the nucleus we have, I believe, a causal expla- 

 nation of the relation between differentiation and senescence. 



The principal objection to Minot's formulation of the cause of 

 senescence is that it overemphasizes the antithesis between nucleus and 

 protoplasm and does not with sufficient clearness distinguish between 

 the general protoplasm and its differentiation products. It is undoubt- 

 edly true that with advancing age and differentiation there is an increase 

 of cellular as compared with nuclear substance, but the significant thing 

 here is the fact that this cellular increase is not so much in the proto- 

 plasm as in the products which are formed from it and which can not 

 enter into the nucleus. 



By all odds the most important structural peculiarity of senescence 

 is the increase of metaplasm or differentiation products at the expense 

 of the general protoplasm. This change of general protoplasm into 

 products of differentiation and of metabolism is an essential feature of 

 embryonic differentiation and it continues in many types of cells until 

 the entire cell is almost filled with such products. Since nuclei depend 

 upon the general protoplasm for their growth, they also become small 

 in such cells. If this process of the transformation of protoplasm into 



"Minot, "Modeme Probleme der Biologic," Fischer, Jena, 1913. 



