1 88 SENESCENCE AND REJUVENESCENCE 



A simple case in point is the accumulation of carbon dioxide 

 which decreases the rate of metabolism in a very short time, while 

 recovery occurs as rapidly when it is eliminated. According to 

 the theory of stimulation by R. S. Lillie ('090, '096), the concen- 

 tration of carbon dioxide in the cell is the chief factor in decreasing 

 the rate of reaction after stimulation. Lillie suggests that in the 

 absence of excitation the plasma membrane of cells is impermeable 

 or only slightly permeable to carbon dioxide, consequently the car- 

 bon dioxide resulting from metabolism accumulates in the cell 

 and decreases the rate of metabolism. A stimulus is any external 

 factor which increases the permeability of the membrane to carbon 

 dioxide and so permits its escape from the cell and consequently 

 brings about an increase in rate of metabolism, which is followed by 

 a decrease in rate as the temporary increase in permeability of the 

 membrane disappears. 



Fatigue, i.e., the decrease in rate of metabolism which follows 

 continued stimulation, is generally believed to be due to the accu- 

 mulation of toxic products of metabolism (see p. 297) . During rest 

 these products are eliminated and recovery occurs. Various meta- 

 bolic intoxications are probably very similar in character, although 

 in many of these cases the toxic substances are the products of metab- 

 olism of micro-organisms and not of the affected organism itself. 

 The decreased metabolic activity which occurs after feeding in 

 many animals is undoubtedly due to accumulation of some sub- 

 stance or substances which decrease the rate of reaction. As the 

 accumulated substance disappears, activity increases until feeding 

 again takes place. 



In these and many other cases the changes in metabolism are 

 readily and rapidly reversible, because the substances or conditions 

 which determine them are readily eliminated or are themselves 

 reversible. Moreover, except where the activity of the cell is 

 largely accumulatory or secretory, these changes are not ordinarily 

 accompanied by any very marked morphological changes. When 

 extreme or long continued, however, stimulation may bring about 

 very considerable structural changes, even in cells where functional 

 activity is largely dynamic rather than structural, such, for example, 

 as the nerve cells, in which the morphology of function has been 



