X-Message-Number: 21365 Date: Sat, 8 Mar 2003 10:18:42 -0800 (PST) From: Doug Skrecky <> Subject: superoxide dismutase mimetic EUK-8 is a bust 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 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=21365