The Mechanisms of Senescence 



change in old ovaries carried by young hosts. Details of this 

 study have not yet appeared. 



In rats semicastrated during old age, Wiesner (1932) found 

 a marked reduction in compensatory hypertrophy of the remain- 

 ing ovary. One major feature of senescence is probably pro- 

 gressive reduction of the ovarian reserve in terms of hormone 

 production. Such an effect, rather than the consumption of 

 ova, may account for the earlier menopause in semicastration 

 (Masters, 1952). Failure of the ovary to respond to pituitary 

 stimulation is almost certainly the proximate cause of the human 

 menopause. (See also Klebanow and Hegnauer, 1949.) 



In rare instances a failure of the menopause itself has been 

 reported — menstruation is said to have persisted in a woman 

 of 104 (Novak, 1921) — but pathological causes were probably 

 responsible for some at least of these cases. 



By far the most interesting fact from the standpoint of sen- 

 escence is the striking increase in pituitary gonadotrophin level 

 at the human menopause, and the comparable but more 

 gradual increase in senile men (Henderson and Rowlands, 

 1938) and rats (Lauson, Golden and Severinghaus, 1939). This 

 not only indicates a change in gonadal tissue reactivity with 

 age, but it also shows how limited senile processes may provoke 

 compensatory reactions and further disturb homoeostasis. Ova- 

 riectomy in certain strains of mice predisposes them to carcinoma 

 of the adrenal cortex, which can be prevented by oestrogens 

 (Woolley and Little, 1946). The senile increase in gonado- 

 trophin closely resembles that which follows castration, though 

 it develops more gradually (in female rats — Lauson, Golden 

 and Severinghaus, 1939). Witschi (1952) found that in women 

 the castrate level of FSH by pituitary gland assay is established 

 very rapidly after the menopause, and persists for the rest of 

 life, while in men the rise is far more gradual, the castrate level 

 being reached only at 70 years and only by a few individuals. 

 In a majority of cases the hypophyseal FSH content either 

 remains at the normal adult level or falls, occasionally even 

 below childhood levels. But in male eunuchs castrated in child- 

 hood, pituitary gonadotrophin output may remain, from the 

 time of normal puberty into middle age, at about ten times the 

 normal level (Hamilton, Catchpole and Hawke, 1944, 1945). 



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