Growth and Senescence 



— there being no evidence that starved rats remain 'young* 

 indefinitely. By 1150 days, moreover, only about half the 

 retarded individuals were capable of resuming growth (McCay, 

 Sperling and Barnes, 1943). There is some evidence from later 

 work that prolongation of the life-span, though in a smaller 

 degree, can be produced by intermittent dietary restriction with- 

 out any evident effect on the growth-rate (Carlson and Hoelzel, 

 1946). Moreover most of the changes which ultimately fix the 

 specific age appear to have occurred at the time of maturity, 

 since the increase in longevity obtained by underfeeding, adult 

 rats is far less (McCay, Maynard, Sperling and Osgood, 1941). 



The mechanism of retardation by dietary restriction in grow- 

 ing mammals is partially known from other studies. Inanition 

 lowers the gonadotrophic activity of the pituitary: this was 

 clearly shown by the transplantation studies of Mason and 

 Wolfe (1930) on female rats, and again in male rats by Moore 

 and Samuels (1931). In rats, reduction of the protein content 

 of the diet below 7 per cent produces anoestrus from gonado- 

 tropin deficiency (Guilbert and Goss, 1932). In the 'pseudo- 

 hypophysectomy' of malnutrition, pituitary growth hormone 

 will re-initiate growth of the skeleton and decrease the rate of 

 weight loss even without increase of food intake (Mulinos and 

 Pomerantz, 1941). The subject was reviewed by Samuels 

 (1946). The relationship between this 'pseudohypophysectomy' 

 and McCay's results is not yet clear, but the effects of restricted 

 food intake on the pituitary probably play a major part in the 

 alteration of apparent specific age. 



In C3H mice, Garr, King and Visscher (1949) produced 

 anoestrus by reducing the standard calorie intake by half: at 

 14 months of age, single cycles were readily induced by admin- 

 istering dextrose, though the dose necessary to bring this about 

 varied from 0-15 to 1-0 gm. When the mice were permitted at 

 the age of 2 1 months to feed at will, and mated, all became 

 pregnant, and 10 out of an initial total of 17 were alive and 

 sexually active at the age of 23 months. 



We have no comparable observations in man. Malnutrition 

 can produce gross retardation of puberty (as can disease or 

 'indirect' malnutrition — the effects of bilharzia are particularly 

 striking) but such malnutrition is always total, and shortens life. 



151 



