130 George A. Sacher 



(b) errors of synthesis and denaturations that occur in the 

 steady state of metabohc activity — the probabihty of produc- 

 ing incorrect molecules per unit time arising from inherent 

 imperfections of the metabolic process (inadequate specificity 

 of enzymes, presence of by-product metabolic poisons, etc.) 

 in the ideal steady state for the species as this is established 

 by natural selection operating on the genetically controllable 

 thermodynamic properties of enzymes ; 



(c) errors in synthesis and denaturations occurring as a 

 result of deviations from the steady state ; 



(d) adventitious poisoning of environmental origin — radi- 

 ation, poisons, etc. (this class will not be discussed here). 



These classes of determiners are distinguishable by the way 

 in which the observed ageing rate (mutation rate, etc.) 

 depends on certain environmental and system variables. 

 Thermal inactivation would operate equally on almost all 

 mammalian species since they have (except for bats and some 

 other forms) essentially the same constant body temperature. 

 Thus thermal denaturation can be ruled out as a factor 

 determining the different rates of ageing in different species. 

 The error rate in the metabolic steady state should have a 

 direct, essentially proportional relation to metabolic rate and 

 in consequence a determinate relation to body mass. Hence, 

 if this is an important factor in determining the rate of 

 accumulation of ageing events one would expect lifespan to 

 vary as an inverse function of metabolic rate. This is the 

 Rubner hypothesis, which was seen above to be in general 

 accord with the data. 



The error rate due to fluctuations away from the steady 

 state would tend to be smaller in species possessing superior 

 physiological regulatory mechanisms, for in these species the 

 mean square deviation from the steady state is smaller. The 

 evidence on this point, deriving from the relation of lifespan 

 to index of cephalization, is indirect but nevertheless persua- 

 sive, as was discussed earlier. 



Thus the comparative, allometric approach has shown us 



