X-Message-Number: 26321
Date: Sun, 12 Jun 2005 05:17:31 -0700 (PDT)
From: Doug Skrecky <>
Subject: superoxide has nothing to do with nematode aging

Free Radic Biol Med. 2004 Jul 15;37(2):239-50.
Superoxide dismutase mimetics elevate superoxide dismutase activity
in vivo but do not retard aging in the nematode Caenorhabditis elegans.
    According to the oxidative damage theory a primary cause of
aging is the accrual of molecular damage from reactive oxygen species
(ROS), particularly superoxide and its derivatives. This predicts that
treatments that reduce ROS levels should retard aging. Using the
nematode Caenorhabditis elegans, we tested the effects on stress
resistance and life span of treatment with EUK-8 and EUK-134, synthetic
mimetics of the antioxidant enzyme superoxide dismutase (SOD), which
neutralises superoxide. Treatment with SOD mimetics elevated in vivo
SOD activity levels, particularly in mitochondria, where up to 5-fold
increases in SOD activity were recorded. Treatment with exogenous SOD
mimetics did not affect endogenous protein SOD levels. Where life span
was reduced by the superoxide generators paraquat and plumbagin, EUK-8
treatment increased life span in a dose-dependent fashion. Yet in the
absence of a superoxide generator, treatment with EUK-8 or EUK-134 did
not increase life span, even at doses that were optimal for protection
against pro-oxidants. Thus, an elevation of SOD activity levels
sufficient to increase life span when it is limited by superoxide
generators does not retard aging in the absence of superoxide
generators. This suggests that C. elegans life span is not normally
limited by levels of superoxide and its derivatives.

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