superoxide dismutase mimetic EUK-8 is a bust

Doug Skrecky oberon at vcn.bc.ca
Wed Mar 26 14:28:51 EST 2003


 No Increase in Lifespan in Caenorhabditis Elegans Upon Treatment With the
 Superoxide Dismutase Mimetic EUK-8.
 Free Radical Biology & Medicine Vol.34, No. 2, pp, 277-282, 2003

 ABSTRACT:     The superoxide dismutase mimetic EUK-8 has been reported to
 extend lifespan in the nematode Caenorhabditis elegans. However, in five
 trials administering EUK-8 in liquid culture with E. coli, and two trials
 using defined liquid medium, we observed no increase in C. elegans
 lifespan.Instead we saw a dose-dependent reduction of lifespan and
 fertility. We conclude that extension of C. elegans lifespan by EUK-8 may
 only occur under very particular culture conditions.

 [comment by poster:]
 Here' a short summary of what does work to increase lifespan in C.
 elegans:
     Interventions that reduce the metabolic rate of C. elegans also
 increase lifespan. (Proc. Natl. Acad. Sci. 96: 11399-11403 September
 1999) Such interventions include reducing environmental temperature,
 genetic alterations such as age-1, or daf-2 mutations, and (probably)
 depletion of coenzyme Q in the diet.
     I had believed that calories were a factor as well, since addition of
 E. coli bacteria to medium, increases nematode size, and reduces
 lifespan. However it has been found recently that lifespan increases
 occur in nematodes that are switched to a medium containing an E. coli
 mutant which does not synthesize coenzyme Q. Thus it would appear that it
 is the coenzyme Q content, rather than calories, which modulates lifespan
 via medium alterations. (see below)

 (Mechanisms of Ageing and Development 6: 413-429 1977)
 Temperature effects
 Degrees C     Average lifespan (days)
 ____________________________________
      6             17.8
     10             34.7
     14             20.8
     16             23.0
     20             14.5
     24              9.9
     25.5            8.9

 (note on 6 C result: Chilling damage can occur at very low temperatures,
 as cell membranes undergo a phase change, and leak cell contents.)

 (Genetics 141: 1399-1406 December 1995)
 Genetic/Temperature effects
 Degrees C  Strain                Mean  Maximum Lifespan (days)
 _____________________________________________________
    15      wild                  25      33
    15      age-1. fer-15         29      60
    15      daf-2                 43      62
    15      daf-2, age-1, fer-15  52      74
    20      wild                  18      28
    20      daf-2                 36      78
    20      daf-2, daf-20         50      83
    25      wild                  12      25
    25      age-1, fer-15         23      41
    25      daf-2                 33      60
    25      daf-2, age-1, fer-15  33      56

 (Science 272: 1010-1013 May 17, 1996)
 More Genetic/Temperature effects
 Degrees C  Strain       Mean lifespan (days)
 ________________________________________
    18      daf-2         29.7
    18      daf2, clk-1   34.0
    25      N2             8.5
    25      clk-1          8.6
    25      daf-2         15.9
    25      daf-2, clk-1  49.1

 (Science 295: 120-123 2002
 Genetic/Temperature/Coenzyme Q effects
 Degrees C  strain      Coenzyme Q  Mean    Maximum lifespan (days)
 _________________________________________________________________
    20      N2            +Q         13        25
    20      N2            -Q         27        41
    25      daf-2(e1370)  +Q         30        46
    25      daf-2(e1370)  -Q         38        54
    25      daf-2, clk-1  +Q         46        68
    25      daf-2, clk-1  -Q         52        84





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