The Mechanisms of Senescence 



Mothes, 1945; cattle — Reece and Turner, 1937) to reach a peak 

 at or about puberty, with a subsequent decline which has never 

 been followed by assay into old age. The decline of general 

 metabolism with increasing age, which has been frequently 

 linked with the decline of growth-capacity as an index of 'phy- 

 siological ageing', appears to involve both a fall in thyroid 

 activity and perhaps a decline in cell response, since thyroi- 

 dectomized rats show no senile decline in heart rate and 2 

 uptake, and old normal rats are decreasingly responsive to 

 thyroxin administration (Grad, 1953). The declining heat- 

 production of ageing human subjects may well be a reflection 

 as much of muscle atrophy as of thyroid involution. 



The results obtained by McCay, using dietary restriction, 

 could be regarded as the consequences of dietary hypophy- 

 sectomy. Such a state of affairs interferes with the production 

 of both growth hormone and gonadotrophin, and its effect is a 

 general slowing of the 'integrating system' of growth + develop- 

 ment. The separation of these systems in mammals is a problem 

 of great interest and considerable practical difficulty. Dietary 

 retardation greatly postpones, but cannot be kept at such a 

 level as to prevent, the onset of oestrus (Asdell and Crowell, 

 1935). McCay, Sperling and Barnes (1943) found that the 

 capacity of retarded rats to resume growth was ultimately lost 

 if retardation was prolonged. Apparently if growth is delayed 

 without differentiation, it may ultimately encounter a block at 

 the cellular level. 



A beginning has been made on the problem of selective inter- 

 ference with mammalian differentiation by the school of Li and 

 Evans (Walker et al., 1952; Asling et al., 1952a, b). Hypophy- 

 sectomy in 6-day-old rats does not arrest the eruption of teeth 

 or the opening of the eyes, but later sexual and pre-sexual 

 development is suppressed. Untreated animals ultimately die 

 from paralysis due to cerebral compression, the brain outgrow- 

 ing the cranium. Rats which survive the postoperative period 

 have been maintained in good health by growth hormone sup- 

 plements. In these supplemented rats, the rate of growth was 

 only slightly less than that of unoperated controls. Skeletal 

 development was normal, but adult organ-differentiation and 

 sexual maturation did not take place. Three such 'metathetelic' 



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