superoxide dismutase mimetic EUK-8 is a bust

From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Sat Mar 08 2003 - 11:19:21 MST

  • Next message: Alfio Puglisi: "Stem cells news"

     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



    This archive was generated by hypermail 2.1.5 : Sat Mar 08 2003 - 11:24:36 MST