MECHANISMS OF LIFE-SPAN SHORTENING 



H. J. MULLER 



Zoology Department, Indiana University, Bloomington, Indiana, U.S.A. 



SUMMARY 



Reasons are presented for concluding that spontaneous ageing is a part of normal 

 development caused, like most other developmental changes, by other factors than 

 permanent genetic alterations such as point-mutation, deficiency, chromosome loss or 

 inactivation, or segregation, even though it does involve the point-wise death of many 

 individual somatic ceUs. These reasons comprise the partial reversibility of natural 

 ageuag, and its independence of ploidy and of other features of chromosome structure. 



Judged by the same criteria, radiation-induced shortening of the life-span is an 

 expression of point-wise losses of individual ceUs that are caused by actual genetic 

 changes. That the changes are for the most part recessive, depending on either point- 

 mutations, deficiencies, or whole-chromosome losses, is sho^\^l bj^ results in Drosophila, 

 Habrobracon, and plant material, when effects on individuals of different ploidy are 

 compared. Tests of diverse kinds carried out with Drosophila having chromosomes of 

 different structural constitution show clearly that the mechanism here at work is that of 

 chromosome loss, caused by radiation-induced chromosome breaks. It is believed that the 

 same basic mechanism accounts also for most of the acute damage that is produced by 

 radiation. 



First let us ask: what causes natural ageing? Although, our ignorance on this 

 question is profound, it is no more profound than our ignorance of what 

 casuses adolescence, or what causes invagination, or any other major stage or 

 feature of development. Development is a continuous process, of which 

 senility forms the last stage, but one that can be delimited only arbitrarily. 

 The average length of life allotted for any given species is a resultant of the 

 past action of natural selection in having fixed it at the possible amomit most 

 conducive to the survival and multiplication of that species as a whole, just 

 as is true of every other normal stage and feature of every type of organism. 

 For death is an event necessary to allow genetic evolution, and some types of 

 organism can profit more than others by postponing death for a relatively long 

 time. These latter types tend to be the ones which, as individuals, can, by 

 living longer, achieve relatively greater cumulative successes on behalf of 

 species survival. Moreover, the fact that the timing of senility is a very labile 

 trait, genetically, is shown by the considerable differences in regard to it in 

 different species, including even some that are rather closely related. 



Not for many years has there been much serious advocacy of the view that 

 development changes in general reflect permanent changes, of the nature of 



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