TETRAHYDROCURCUMIN PROLONGS SURVIVAL CURVES OF MALE C57BL MICE
K.Kitani1*, T. Osawa2
1National Institute for Longevity Sciences, 36-3, Gengo, Morioka-cho, Obu-shi, Aichi 474-8522, 2Graduate School of Bioagricultural Sciences, University of Nagoya, Furo-cho, Chikusa-ku, Nagoya 464-8600, Japan.
Tetrahydrocurcumin (TC)1 is a metabolite of an antioxidant, curcumin (C) contained in turmeric and is a more potent antioxidant than C itself. A number of studies have shown that TC is effective in preventing pathologies of experimentally induced models of age-associated disorders such as colon2 and breast3 cancer, renal injury4, cataracts, etc. However, no data are available on its effect on animal survivals. We attempted to clarify whether a long term feeding of TC can modify survivals of animals.
Male C57BL/6J mice were purchased from Harlan-Spraque Dawley and were fed TC containing pellets (0.2%) or standard pellets (MF. Oriental Ltd., protein 23.8%) with no TC. Two series of studies were conducted; 1, starting TC or standard feeding at the age of 19 months or 2, at the age of 13 months. Five animals were housed per cage and all animals were carefully raised in clean conventional animal facilities until they died.
In mice which started to receive TC at 19 months, TC fed animals survived slightly longer than controls (mean lifespan 3%, 10% longest survival 5%). However no significant difference was found between control and TC fed mice in terms of average life span as well as 10% longest survival (P>0.05, unpaired t-test). In the second experiment with TC feeding beginning in the 13th month, the difference in survival curves between control and TC fed groups was greater throughout their lives in comparison with that in the first experiment. As the age advanced this difference became more pronounced, yielding more than two-fold differences in survival rates between the control and TC fed groups in age ranges from 29 to 32 months. Values were significantly different between the two groups at ages from 29 to 31 months (P<0.05, Chi-square test). The average life span (days) was 11% longer in TC fed animals, the difference being highly significant (797.6 ± 151.2 vs. 882.2 ± 154.6, mean ± SD, each n=50, P<0.01, unpaired t-test). The 10% longest survival was also significantly longer in TC fed animals than controls (1040.8 ± 24.8 vs. 1108 ± 33.5, each n=5, P<0.05, t-test).
Past trials using a similar design feeding animals with a number of different antioxidants were mostly unsuccessful in significantly modifying survivals of animals (e.g. Ref.5). However, the results of the present study suggest that this type of antioxidant strategy can prolong survivals of animals, when appropriate antioxidants are used with the appropriate timing and dose. This study also suggests that for this type of experimental design it may be more important to monitor survivals of a rather late period of animal lives than to simply compare 50% survival times5. Further a positive result of the second study suggests that an even earlier beginning of TC feeding may provide still better results than in the present study yielding an even longer average life span of animals given TC.
1) Osawa T. et al., Biosci Biotech Biochem 59:1609-12, 1995. 2) Osawa T. et al., Carcinogenesis 19:81-5, 1998. 3) Inano H. et al., Carcinogenesis 20:1011-8, 1999. 4) Okada K. et al., J Nutr 131:2090-5, 2001. 5) Lipman RO. et al., Mech Ageing Dev 103:269-84, 1998.
Key words:
tetrahydrocurcumin, mice, survival, antioxidant strategy
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