caloric restriction, temperature and cancer

Doug Skrecky (oberon@vcn.bc.ca)
Thu, 9 Jul 1998 02:47:10 -0700 (PDT)

Authors
Koizumi A. Wada Y. Tuskada M. Kayo T. Naruse M. Horiuchi K. Mogi T. Yoshioka M. Sasaki M. Miyamaura Y. Abe T. Ohtomo K. Walford RL. Institution
Department of Hygiene, Akita University School of Medicine, Japan. koizumi:med.akita-u.ac.jp
Title
A tumor preventive effect
of dietary restriction is antagonized by a high housing temperature through deprivation of torpor.
Source
Mechanisms of Ageing & Development. 92(1):67-82, 1996 Nov 29. Abstract
Energy restriction (ER) has proven to be the only effective means of retarding aging in mice. The mechanisms of multiplicity of effects of ER on aging remain, however, fragmentary. ER induces daily torpor, the induction of which is reduced by increasing the ambient temperature to 30 degrees C. The effects of preventing hypothermia in ER animals were studied in terms of the expected consequences of ER on survival, disease pattern and a number of physiological parameters in autoimmune prone MRL/lpr mice and lymphoma prone C57BL, 6 mice. The results demonstrate that torpor plays a crucial role in the prevention of lymphoma development but does not have an affect on other aspects of ER, such as prevention of autoimmune diseases.

Additional data added here by the poster:

Mortality data for the autoimmune MRL strain and the lymphoma prone C57BL strain of mice are as follows: (data derived from table 1)

                     Survival (days)     Percentage alive
                     75%   50%   25%       at 1300 days
 ________________________________________________________
 MRL     Control    167   205   255            0%
         Cntl/30C   170   213   230            0
         CR         217   269   519            8
         CR/30C     201   284   340            0

 C57BL   Control    559   778   880            0
         CR         941  1143  1264           19
         CR/30C     739   810  1049            0

Storage temperature had no effect on early autoimmune related MRL mortality, which was mostly cerebral hemorrhage, subarachnoid hemorrhage and rupture of aortic aneurysms. However later mortality was reduced in calorie restricted MRL mice stored at room temperature as opposed to those stored at 30C. Presumably this is due to the anticancer effect of CR induced hyperthermia, which is antagonized by elevated storage temperatures.
Storage at 30C largely reversed the early antilymphoma effect of CR in C57BL mice, reducing the 47% increase in the 50% survival found in CR mice to just 4% for the CR/30C group.
The survival for control C57BL mice varies dramatically from experiment to experiment. In one control group from (Experimental Gerontology 15: 237-258 1980) the 50% survival was about 960 days, which is roughly midway between the CR and CR/30C groups in the present experiment. Variations in temperature regulation of the laboratory may account for some of these differences.