The Mechanisms of Senescence 



ages, or from more recent work such as that of Payne (1949, 

 1952) on the ageing fowl. 



If there has been a tendency for the existence of the pituitary 

 gland to serve as a pretext for vagueness of thought concerning 

 the nature of senescence in mammals — the function formerly 

 discharged by the pineal in the search for the seat of the soul 

 — there are also solid arguments for its direct involvement, 

 certainly as mediator, but possibly also as originator, of senile 

 processes. Because the pituitary is profoundly concerned with 

 several processes of homoeostasis, and is involved with morpho- 

 genetic timing mechanisms like that which initiates puberty, it 

 is easy to develop hypotheses of pituitary senescence which do 

 not depend upon an unbiological argument in terms of single 

 hormones. 



The function of trophic hormones appears to be the provision 

 of one limb of a system of negative feedback, by which the level 

 of effector-organ secretion is maintained and kept constant. If 

 senescence be regarded as a continuously self-aggravating dis- 

 equilibrium (a positive feedback process), then such a process 

 can be induced in a model control system, normally dependent 

 upon negative feedback, by several types of change. 



Consider a system in which a device A produces a signal 

 which increases the activity of a second device B, and in which, 

 at the same time, the activity of B produces a signal which 

 reduces the activity of device A. The properties of most self- 

 regulating biological systems can be reproduced in this model 

 by varying the characteristic of the stimulus A — > B or the 

 negative feedback B — > A, and the number of stable states of 

 A or B. If there is no time-lag in either of these processes, the 

 level of output B will tend to be constant and self-restoring. If 

 there is an appreciable time-constant in one limb of the circuit, 

 the system will tend to function as a relaxation oscillator. In 

 this case, A stimulates B, which does not immediately respond. 

 Stimulus A — > B continues to increase, reaching a level which 

 corresponds to an ultimate response in B sufficient to inhibit A 

 completely. The output of B then declines, permitting A to 

 recover, and this represents one whole cycle. It is a requisite 

 for the functioning of such a system that the unmodified output 

 of A shall tend to increase in the absence of output B, i.e. that 



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