X-Message-Number: 23399
Date: Sat, 7 Feb 2004 20:59:48 -0800 (PST)
From: Doug Skrecky <>
Subject: Free Radical Theory of Aging proven false

Physiol Genomics. 2003 Dec 16;16(1):29-37.
Life-long reduction in MnSOD activity results in increased DNA damage and
higher incidence of cancer but does not accelerate aging.

	Mice heterozygous for the Sod2 gene (Sod2+/- mice) have been used
to study the phenotype of life-long reduced Mn-superoxide dismutase
(MnSOD) activity. The Sod2+/- mice have reduced MnSOD activity (50%) in
all tissues throughout life. The Sod2+/- mice have increased oxidative
damage as demonstrated by significantly elevated levels of
8-oxo-2-deoxyguanosine (8oxodG) in nuclear DNA in all tissues of Sod2+/-
mice studied. The levels of 8oxodG in nuclear DNA increased with age in
all tissues of Sod2+/- and wild-type (WT) mice, and at 26 mo of age, the
levels of 8oxodG in nuclear DNA were significantly higher (from 15% in
heart to over 60% in liver) in the Sod2+/- mice compared with WT mice.
The level of 8oxodG was also higher in mitochondrial DNA isolated from
liver and brain in Sod2+/- mice compared with WT mice. The increased
oxidative damage to DNA in the Sod2+/- mice is associated with a 100%
increase in tumor incidence (the number of mice with tumors) in old
Sod2+/- mice compared with the old WT mice. However, the life spans (mean
and maximum survival) of the Sod2+/- and WT mice were identical. In
addition, biomarkers of aging, such as cataract formation, immune
response, and formation of glycoxidation products carboxymethyl lysine
and pentosidine in skin collagen changed with age to the same extent in
both WT and Sod2+/- mice. Thus life-long reduction of MnSOD activity
leads to increased levels of oxidative damage to DNA and increased cancer
incidence but does not appear to affect aging.

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