LIFE-SPAN SHOKTENING FROM VARIOUS TISSUE 



INSULTSf 



H. J. CURTIS AND CATHRYN CROWLEY 



Biology Department, Brookhaven National Laboratory, Upton, New York, U.S.A. 



SUMMARY 



From experiments in mice, it is shown that a specific organ stress, mercury poisoning 

 of the kidney, can cause irreparable damage which persists indefinitely. The animal is able 

 to compensate for this damage when it is young, but as it ages it fails to compensate and 

 death follows. Tissue scarring is apparently one of the important factors in the ageing 

 process. 



One of the proposed hypotheses of the agemg process is that the various 

 organs of the body can recover only partially from a tissue insult, and death 

 finally results from the accumulation of such insults. The life-span shortening 

 caused by radiation would thus be due to its action as a non-specific stress. 

 To test this theory a rather extensive series of experiments was undertaken 

 (Curtis and Healey, 1956; Curtis and Gebhard, 1959) employing various non- 

 specific chemical stresses. Single, large, just sublethal doses of typhoid toxoid 

 and nitrogen mustard failed to produce any shortening of the life-span, 

 whereas a comparable dose of radiation caused marked shortening. In the 

 belief that perhaps there was not enough of a tissue insult to cause appreciable 

 life-span shortening, these and other toxic agents were administered repeatedly 

 over a large fraction of the life-span of the mice. These included intraperi- 

 toneal injections of turpentine every 14 days, intraperitoneal injections of 

 nitrogen mustard three times a week, subcutaneous injections of tetanus 

 toxin and also tetanus toxoid every 14 days, intraperitoneal injection of 

 typhoid vaccine twice weekly, and others. All these demonstrated that these 

 non-specific stresses cause no appreciable shortening of the life-span. If the 

 animals were able to withstand the stress and recover from it, their life- 

 expectancy was not shortened even though they were kept under severe 

 stress for most of their lives. 



These experiments do not give information on the action of an organ- 

 specific toxin. It is reasonable to suppose that if one vital organ is severely 

 damaged, it might form a "weak link", causing death predominantly by 

 ultimate failure of that organ. The organ chosen for the j)resent study was the 

 kidney. 



t Research carried out at Brookhaven National I>aboratory under the auspices of the U.S. 

 Atomic Energy Commission. 



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