132 Franz J. Kallmann 



defined as a gradual loss of ability to maintain a constant 

 level of physiological equilibrium. Hence, it is the ability to 

 withstand the ensuing impairment of health that determines 

 survival to an advanced age. This capacity is known to be so 

 variable that the many observed differences from one person 

 to another strongly indicate the operation of gene-controlled 

 phenomena (Kallmann, 1956 a and b; Kallmann, Aschner and 

 Falek, 1956). That the potentiality for a long life, derived 

 from a fortunate combination of health-conferring genes, can 

 be modified by adverse life conditions in no way lessens the 

 significance of this fundamental biological hypothesis. 



Genetically, a distinction is made between the effects of 

 gene-specific processes causing premature or other pathological 

 disturbances in the last sector of the human life cycle, and 

 those of general genetic phenomena which produce differences 

 in basically positive health and survival values (Kallmann, 

 1953). The symptoms observed in the first group of disorders 

 are likely to be the result of one major mutant gene that follows 

 the single-factor type of inheritance. 



Seen in the second group of variable patterns of adjustment 

 are gradations in normal ageing potentials which result from 

 the interaction of several or many genes and are therefore 

 ascribable to the multifactor or polygenic mode of inheritance. 

 Extreme variations determined in this manner (through the 

 accumulation of short-life genes) are apt to produce deviations 

 from the mean health status of an ageing population, which 

 are classifiable as pathological. Some of these deviations may 

 be so clearly pathological as to be indistinguishable from 

 either a single-factor type of disturbance or a so-called pheno- 

 copy (a non-hereditary variation simulating the phenotype of 

 a mutant gene). 



Still another group of minus variations in adjustment to 

 ageing is due to gene-controlled deficiency states, physical or 

 mental, which arise before the senescent period but tend 

 incidentally to alter the adaptive plasticity of ageing persons. 

 In this category are the major psychoses, specific metabolic or 

 endocrinopathic disorders, and various types of intellectual 



