...cite this piece of evidence to him/her and ask if he/she understands where most of the lipid peroxidation originates:
Ann N Y Acad Sci. 1996 Jun 15;786:24-43.
Simultaneous increase of mitochondrial DNA deletions and lipid
peroxidation in human aging.
Wei YH, Kao SH, Lee HC.
Department of Biochemistry, School of Life Science, National Yang-Ming
University, Taipei, Taiwan, Republic of China.
Human mtDNA is a naked circular double-stranded DNA, which is
continually exposed to the matrix that contains high levels of ROS and
free radicals. High oxidative stress and a lack of proofreading during
mtDNA replication and efficient DNA repair mechanisms in the
mitochondria have rendered mtDNA extremely vulnerable to oxidative
damage. More than one dozen large-scale deletions in mtDNA have been
identified in various tissues of old humans. The 4,977-bp and 7,436-bp
deletions are the most prevalent and abundant ones. The onset age of
various mtDNA deletions varies greatly with tissues of each individual
and type of deletion. In this and previous studies, we have
demonstrated with PCR techniques that the frequency of occurrence and
the proportion of the 4,977-bp and 7,436-bp deleted mtDNAs are
significantly increased with the age of the human. The mtDNA deletions
are not detectable in any tissues from young healthy subjects or blood
cells from normal individuals of any age, which indicates that the
deletions are generated and accumulated only in postmitotic cells upon
aging. Moreover, we found that these mtDNA deletions occur more
frequently and abundantly in tissues with high energy demand (e.g.,
muscle) as compared to those with low energy demand. On the other
hand, we found that the amount of lipid peroxides measured as
malondialdehyde and the activity of manganese-superoxide dismutase in
the mitochondria exhibit an age-dependent increase in various human
tissues. The lipid peroxide level in muscle was significantly higher
than that in the other tissues. Moreover, we found a positive
correlation between the proportion of the 4,977-bp deleted mtDNA and
lipid peroxide content in the mitochondria of human tissues during
aging. Muscle the tissue of high energy demand, was found to be more
vulnerable to oxidative damage that lead to most abundant mtDNA
deletions and lipid peroxidation among all the tissues examined.
Taking these results together, we suggest that the enhanced generation
of reactive oxygen species and lipid peroxides in the mitochondria
during the aging process occur simultaneously with large-scale
deletions and the other types of mutations in mtDNA, which are early
molecular events and major contributory factors of human aging.
PMID: 8687024 |
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