The Biology of Senescence 



Polovny, 1942). All the general characters of tissue behaviour 

 during the attainment of specific size appear to be exemplified 

 in liver. These include (1) negative specific acceleration of 

 growth, (2) retention of growth capacity after the limiting size 

 has been attained, as demonstrated either by explants, or, in 

 this case, following partial removal of the organ, (3) increased 

 growth inertia with increasing age and (4) 'post-inhibition 

 growth rebound'. Medawar (1942) stresses the surprisingly wide 

 distribution of this last effect, which is shown by tissue cultures 

 (Spear, 1928) and Ambly stoma larvae (Buchanan, 1938) retarded 

 by cooling, and in rats or mice following brief restriction of diet 

 (Osborne and Mendel, 1916; Clarke and Smith, 1938; Jackson, 

 1936). 



Much has been made of the decline in rate of wound healing 

 with age proposed by du Noiiy (1916, 1932) as a criterion of 

 senescence. This entire theory was based on less than a dozen 

 uncontrolled cases. Experimental studies suggest that while the 

 mitotic rate in wounded skin is highest in infancy, little differ- 

 ence in cell multiplication exists between adult and senile 

 animals, though here again the time-lag in reaching the peak 

 mitotic rate increases with age (Howes and Harvey, 1932; 

 Bourliere, 1950. Delayed healing of skin wounds is not clinic- 

 ally very evident in old people (Elman, 1953). In male mice 

 the mitosis curve for skin in situ is bimodal, with peaks in infancy 

 and again in middle age (Bullough, 1949). One easily-measured 

 growth-system which shows a steady decline throughout later 

 life is that controlling fingernail growth (Knobloch, 1951; 

 Burger, 1954). 



Attempts have been made in the specific case of liver tissues 

 to relate organ size to the existence of a mitotic inhibitor or 

 inhibitors. Studies on plasmapheresis (Glinos and Gey, 1952) 

 and parabiosis (Bucher, Scott and Aub, 1950) after partial 

 hepatectomy have yielded some evidence that a humoral 

 inhibitor, of the kind envisaged by Carrel and Ebeling (1921) 

 disappears from circulation after hepatectomy. These observa- 

 tions, though interesting, could provide a suspiciously simple 

 picture of the dynamics of growth limitation, and of consequent 

 senescence. 



An opposing view to the humoral school has been suggested 



156 



