X-Message-Number: 24178
Date: Tue, 1 Jun 2004 19:23:39 -0700 (PDT)
From: Doug Skrecky <>
Subject: are mitochondria important in aging, or not?

(From the two abstracts quotes below, one could reach diametrically
opposite conclusions.)

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.

Reduced Mitochondrial Function Important Mechanism In Aging
Scientists at the Karolinska Institute have found that changes in the
"powerhouse" of cells, the mitochondria, play a key role in aging. The
findings are being published in this week's issue of the journal Nature.
Mitochondria, which provide energy to cells, have their own set of DNA.
Mutations of mitochondrial DNA increase with age, but until now no one
knew whether this is a result of aging or a cause of aging. New research
findings now indicate that the latter is the case. Mice with a deficient
capacity to correct mutations in mitochondrial DNA acquired an increased
number of mutations and proved to age considerably earlier than normal.
They lived an average of 10 to 12 months compared with the normal 2 or 3
years. These mice also developed several typical signs of premature aging,
such as osteoporosis, weight loss, hair loss, anemia, reduced fertility,
and heart muscle disorders. The findings reveal fundamental biological
mechanisms that lie behind the aging process. This knowledge paves the
way for the possibility of slowing down aging and treating pathological
changes that arise in connection with aging by protecting mitochondrial
DNA from damage.
The article is published in Nature, May 27, 2004, pp. 417-423. It is
illustrated by a picture on the cover of Nature and commentated by two
scientists from the University of Washington, Seattle.
Publication: Premature aging in mice expressing defective mitochondrial
DNA polymerase Nature (2004) 429: 417-423,

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=24178