064 GROWTH AND THE AGING PROCESS I4 



In relation to the problems of protein synthesis it is interesting to note that one 

 type of cell, the neuron, while not actively "growing", still shows evidence of 

 constant production and using up of protein during its functional activity. This 

 has been shown to be true not only for cells which have been undergoing exhaustive 

 activity (Hyden, 1943, 1944, 1945, 1947) but also for those carrying out entirely 

 normal function (Hyden and Hamberger, 1945). The organization of the nerve 

 cell seems to be determined by the necessity for its being ready to produce 

 protein rapidly whenever called upon to do so. While these recent studies have 

 made excellent use of the quantitative methods of photoelectric microspectro- 

 graphy, much credit should be given to the early studies by Dolley (1909a, b, 

 191 1, 1 91 2, 1 91 7 a,b) in which the cytological stages of functional activity, exhaus- 

 tion, and recovery of the nerve cell were worked out in great detail. 



By the time that growth has to all effects ceased in the multicellular organism 

 the histological appearance of the tissues is considerably different from that seen 

 in the rapidly growing phase. The concentration of nucleotides is much reduced 

 and the nucleoli, except in certain types of cells where rapid protein synthesis is 

 a part of normal function, have become much less conspicuous. Mitotic figures 

 are very scarce in the tissues of the mature body. To return to our analogy, we 

 may say that from this time on through middle age the stream of life has reached 

 a relatively stagnant condition. The results of this stagnation upon the individual 

 tissues and cells begin to appear at the inception of senescence. 



This is not the place to present a detailed description of the changes found in 

 the tissues of senile organisms. We have attempted to summarize the work on this 

 subject in a monograph (Andrew, 1952) and in recent papers (Andrew, 1956a 

 and 1956b). However it is pertinent to consider here how the microscopic appear- 

 ance of the tissues in the rapidly growing phase, in the mature condition, and in 

 senescence compare with one another. We have mentioned the visible indications 

 of rapid growth in embryonic and in regenerating tissues. In the mature organism 

 the general picture is one of stability, of a retention of the "typical" histological 

 picture of the organ, whether it be liver, kidney, salivary gland, thyroid gland, 

 spleen, lymph node, or brain. 



In the senescent organism we have found changes in all of these organs, con- 

 sistent in type for any one organ, but differing considerably with the type of organ. 

 Thus, in the liver the appearance of numerous scattered large hepatic cells with 

 enormous nuclei, a much increased number of nucleoli, and often intranuclear 

 inclusions, is conspicuous (Andrew, Brown and Johnson, 1943) (Fig. 6). In 

 the kidney accumulation of colloid in the tubules with considerable atrophy 

 of fining epithelium is seen (Andrew, 1955b). In the parotid gland great 

 masses of the secreting parenchyma undergo fatty degeneration (Andrew, 1 949) 

 (Fig. 7A). 



In the thyroid gland a marked deterioration of follicles occurs and fibrosis is a 

 prominent feature (Fig. 8A and B). In the spleen and lymph nodes there is a loss 

 of germinal centers (Andrew, 1946) and in the lymph nodes an appearance of 

 fluid-filled cysts or a replacement of lymphoid tissue by adipose or fibrous tissue 

 (Andrew, 1948). In the brain we have found changes in the individual cells in 

 many areas (Andrew, 1936, 1937, Andrew and Cardwell, 1940) (Figs. 9 and 10) 



