The Biology of Senescence 



the state of A is inherently unstable. If output A be assumed to 

 be the pituitary gonadotrophin and output B the gonadal 

 hormone, then the immediate response of the pituitary to 

 castration, or senile decline in gonadal response, is of the un- 

 stable type, though other mechanisms operate later to restore 

 regulation. Where, as may be the case in the male, the pituitary- 

 gonad balance operates as a level-control, gradual failure of 

 B's response would be expected to cause a gradual increase in 

 output A. In a similar system containing a time-constant, and 

 therefore behaving cyclically, blocking would be expected to 

 occur at one point in one particular cycle, with a proportion- 

 ately greater rise in output A. 



The importance of this homoeostatic concept is that in the 

 simplified model self-regulating equilibrium can be turned to 

 progressive disequilibrium by several types of change. Decline 

 in the capacity of either A or B to respond to B — > A or A — > B 

 will result in a permanently unstable state of A. If the response 

 of A fails, B will also be driven into maximum output. Decline 

 in the capacity of B to produce B — > A will induce the un- 

 stable state of A. Decline in the capacity of A to produce A — > B 

 will lead to the relapse of B into its stable state of zero output. 

 This, however, where B's output effects other systems, will 

 cause disequilibrium in a complex physiology. In addition to 

 these purely quantitative changes, biological cybernetic mech- 

 anisms are also capable of exhibiting, and, in development, 

 characteristically do exhibit, qualitative change in the specifi- 

 city both of signal and response, which further complicates the 

 picture. 



Although analogies from circuits oversimplifying the reality 

 of mammalian homoeostasis, they indicate the number of 

 variables to be considered in studying the senescence of homo- 

 eostatic systems; and they indicate some of the ways in which 

 such senescence can be analysed. Evidence suggests that in the 

 case of the gonad it is the function of B which declines. With 

 the pituitary trophic hormones, other than the gonadotrophins 

 and ACTH, in vivo estimation of levels, corresponding to the 

 measurement of output A, cannot as a rule be carried out. The 

 action of these homoeostatic systems, moreover, is not expressed 

 through static components but through a developing organism 



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