The Mechanisms of Senescence 



The relation of these changes and their reversal to the general 

 picture of senescence in mammals remains extremely obscure. 

 Of the more general processes in which gonadal hormone with- 

 drawal plays a part, few have been identified with certainty. It 

 has been suggested, for instance, that the osteoporosis of old age 

 is a result of the withdrawal of gonadal anabolic hormones 

 (Allbright, 1947). All theories of gonadal action in senescence 

 have, however, to accommodate the probability that in mammals 

 senile change in the force of mortality of apparently typical form, and at 

 approximately the typical specific age, occurs in both sexes in the absence 

 of both gonads, regardless of the age at which these are removed. 



The mechanisms which fix the timing of puberty, and of the 

 human menopause, are the most obvious of all mammalian age 

 processes, and quite the most promising experimentally. The 

 key problem is to determine whether the timing-factors reside 

 primarily in the gonadal cells or elsewhere. The application of 

 transplantation techniques to this question has been reviewed 

 by Krohn (1955). Unfortunately, it already appears likely that 

 there are considerable interspecific differences. The ability of 

 the gonadal cells in situ to respond to gonadotrophin has some- 

 times been regarded as controlling the onset of puberty. 

 Pituitary gonadotrophin is detectable in the hypophysis of the 

 17 cm. pig foetus (Smith and Dortzbach, 1929) and the im- 

 plantation of glands from 3-month-old rabbits is as effective in 

 inducing puberty as implantation of adult glands (Saxton and 

 Greene, 1939). The ovaries of immature rabbits do not respond 

 to injected gonadotrophin (Hertz and Hisaw 1943, Parkes 

 1942-44, Adams 1953) On the other hand, it has long been 

 known that when ovaries are transplanted reciprocally be- 

 tween young and old animals, it is the age of the recipient 

 before or after puberty, not that of the ovary, which determines 

 function or non-function (Foa, 1900, 1901; Long and Evans, 

 1922) and in some species gonadotrophin readily induces pre- 

 cocious ovarian and testicular development. Domm (1934) was 

 able to induce crowing at 9 days of age and treading at 13 days 

 in cockerel chicks by injections of pituitary gonadotrophins. 

 The timing-mechanism is stable within a species or a genetic 

 strain. Human puberty very exceptionally occurs during child- 

 hood without any obvious pathological cause ('constitutional 

 n 179 



