NON-SPECIFIC LIFE-SHORTENING 275 



Unpublished results show that there was similarly no additive or syner- 

 gistic effect of whole-body irradiation by fast neutrons and natural ageing. 



Any study of ageing processes which uses time of death as the measure of 

 the amount of ageing must face the problem of how to allow for the "accidental" 

 aspects of death. Thus unirradiated reciprocal hybrid A x CBA and CBA x A 

 female mice die at very different ages: their life-spans are in the ratio 2 : 3. 

 The two kinds of mice are genetically identical except for some parts of their 

 sex chromosomes and this should give pause to those who attribute differences 

 in life-span to genetic differences and the life-shortening effects of radiation to 

 induced genetic change. | Taking this suggestion seriously (and ignoring 

 additional information gained by examining individual organisms for 

 possible causes of death) entails the conclusion that sex chromosomes are far 

 more important than autosomes in determining life-span, a conclusion which 

 is at variance with the basic idea that gross loss of genetic information is the 

 determining factor in cellular and organismal ageing. 



Actually the difference in life-span of the two hybrids is due to a specific 

 lesion, the murine mammary tumour, and the reason why normally one 

 hybrid and not the other suffers from the tumours, although both are equally 

 susceptible, is that the A x CBA hybrid derives a transmissible cell-free 

 agent (virus) from its mother's milk whereas the CBA mother of the other 

 hybrid does not carry the virus. Thus in this case the life-span depends not 

 on chromosomal or genetic constitution but on the "accident" of infection. 



REFEEENCES 



Mole, R. H. (1962). In "Some Aspects of Internal Irradiation" (T. F. Dougherty ed.). 



Pergamon Press, Oxford. 

 Mole, R. H., and Thomas, A. M. (1961). Radiation Res. 14, 487. 



DISCUSSION 



ROTBLAT: First of all, I would like to say that the results of Dr. Mole don't disagree with 

 our results; slight differences may be explained by the fact that we used a different 

 strain of mice. The interesting thing is that if you take a look not at the absolute shorten- 

 ing of life-span but express it as a proportion of the potential life-span, then it turns out 

 that the variations with age are much less, and it follows almost exactly in relation to 

 age. I would like someone to check Dr. Mole's results with different radiations as well. 

 mole: First of all I did show, in one slide anyway, that the proportional hfe-shortening, 

 also got less the older the animal, from 40 to 10%, quite a substantial change. Secondly, 

 I don't think that these results necessarily disprove a non-specific life-shortening but 

 what they do seem to show is that radiation and natural ageing don't add. This I think 

 is very difficult to swallow if you think they have the same mechanism. 

 ROTBLAT: Well, we may have been lucky there, but I don't think people can say they add 

 but they act in a similar fashion, this is what people can say but we are sure that they 

 carmot be identical because they have produced different results. They may act in a 

 similar fashion but it doesn't necessarily follow that they must be additive. 



f See H. J. MuUer, "Mechanisms of Life-span Shortening", this volume. 



