1 84 SENESCENCE AND REJUVENESCENCE 



Such changes are most conspicuous in those cells which become 

 loaded with non-protoplasmic inclosures, such as granules or 

 droplets, or in which the cytoplasm is largely transformed into the 

 inactive substance of skeletal or supporting tissues, but it is evident 

 that similar changes occur to a greater or less extent in all cells 

 during differentiation. Development must then be accompanied 

 by a progressive decrease in the rate of metabolism per unit of 

 weight or volume of the substance of the organism. 



But other factors are probably more or less generally concerned 

 in bringing about the decrease in metabolic rate which occurs 

 during development. It is a familiar fact that emulsoid colloid 

 sols and gels outside the organism undergo changes in aggregate 

 condition with time. The degree of aggregation increases, the 

 water-content decreases, and shrinkage occurs. To what extent 

 such changes occur in the colloids of the living organism is a ques- 

 tion, but that there is more or less change of this sort in the more 

 stable portions of the colloid substratum is highly probable, and in 

 any case the continued accumulation of colloids in the cell as a 

 product of metabolism probably brings about an increase in con- 

 centration and of aggregation in the colloid. The rate of chemical 

 reaction in a colloid substratum is more or less intimately associated 

 with the condition of the colloid and very generally decreases with 

 increasing aggregation. The increasing density and aggregation of 

 the colloid substratum may lead, then, to an actual decrease in the 

 rate of chemical reactions. Moreover, the increase in density and 

 thickness and the decrease in the permeability of membranes may 

 retard the exchange through them. The retardation of enzyme 

 activity by accumulation of the products may also play a part in 

 decreasing metabolic rate, though it is probable that such decreases 

 in metabohc activity are usually less permanent than the age 

 changes and are associated with other shorter periods in the Hfe 

 of the organism. Various other factors, as yet unrecognized, 

 may also be concerned, but it is evident in any case that the decrease 

 in rate of metabohsm is a part of development itself and not an 

 accidental or incidental feature of life. The decrease in metaboUc 

 rate during development is in fact a necessary and inevitable 

 consequence of the association of the chemical reactions which 



