190 G, W. CASARETT 



According to ideal concepts, an agent is regarded as causing premature 

 ageing if it causes the force of age-dependent mortality to increase earlier 

 in the treated than in the non-treated control popidation, brings forward in 

 time the age of onset of diseases which aifect the controls, without altering 

 the sequence or the incidence of diseases and causes of death, and causes 

 characteristic morphological and physiological manifestations of the ageing 

 process to appear and develop at proportionately earlier chronological ages. 



If the agent causes these manifestations to develop prematurely, but does 

 not alter their rate of development thereafter, the effect is simply one of 

 'precocious ageing. If the agent causes also an increase in rate of development 

 of the manifestations, the effect is not simply precocious but one of accelera- 

 tion of ageing. 



MOKTALITY DATA 



With increasing age in the adult there is generally a progressive increase 

 in the probability of disease and accident and in the probability of death. 



Inherited body constitution establishes essentially the baseline in an 

 individual with respect to the ageing process and its rate and the maximal 

 life-span even under optimal conditions. 



However, a comparison of mean or median longevities alone is meaningless 

 in terms of the process or rate of ageing, since many age-independent factors 

 are capable of reducmg or increasing the median or mean life-span of a 

 population. Comparison of the temporal distribution of death is a little more 

 meaningful but still very limited in usefulness with respect to assessment of 

 the ageing process. 



For a group of mammals maintained under excellent environmental 

 conditions the shape of the arithmetic survival or mortality curve tends 

 toward the rectangular (Fig. 1, A), indicating a relatively low incidence of 

 age-independent causes of death. At the other extreme, a group of mammals 

 kept under poor environmental conditions and subject to a very higli incidence 

 of age-independent causes of death, with few living to senescence, exhibits an 

 arithmetic survival curve which resembles a logarithmic decay curve (Fig. 

 1, D). When multiple life-shortening factors independent of age modify an 

 arithmetic rectangular survival curve they tend to reduce it in the direction 

 of a straight line (Fig. 1, B and C) or, if the effect is marked, toward the 

 logarithmic decay curve (Comfort, 1959). 



Combinations of the effects of premature ageing and of increases or 

 decreases in incidence of age-independent causes of death at various times 

 in the life-span can result in survival curves of many shapes. Furthermore, 

 when an agent is capable of producing a prophylactic or therapeutic effect in 

 relation to any serious age-independent or age-dependent disease in a popula- 



