Of some interest in relation to Rafal's paper?
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Exp Gerontol. 2005 Nov 20; [Epub ahead of print] Related Articles,
Links
Estimation of the mtDNA mutation rate in aging mice by proteome
analysis and mathematical modeling.
Mao L, Zabel C, Wacker MA, Nebrich G, Sagi D, Schrade P, Bachmann S,
Kowald A, Klose J.
Institute for Human Genetics, Charite, University Medicine Berlin,
Berlin, Germany.
The accumulation of mitochondria containing mutated genomes was
proposed to be an important factor involved in aging. Although the
level of mutated mtDNA has shown to increase over time, it is currently
not possible to directly measure the mtDNA mutation rate within living
cells. The combination of mathematical modeling and controlled
experiments is an alternative approach to obtain an estimate for the
mutation rate in a well-defined system. In order to judge the relevance
of mitochondrial mutations for the aging process, we used a mouse model
to study age-related alterations of the mitochondrial proteins. Based
on these experimental data we constructed a mathematical model of the
mitochondrial population dynamics to estimate mtDNA mutation rates.
Mitochondria were isolated from mouse brain and liver at six different
ages (newborn to 24-months). A large-gel 2D-electrophoresis-based
proteomics approach was used to analyze the mitochondrial proteins. The
expression of two respiratory chain complex I subunits and one complex
IV subunit decreased significantly with age. One subunit of complex III
and one subunit of complex V increased in expression during aging.
Together, these data indicate that complex I and IV deficiency in aged
tissues might be accompanied by feedback regulation of other protein
complexes in the respiratory chain. When we fitted our experimental
data to the mathematical model, mtDNA mutation rate was estimated to be
2.7x10(-8) per mtDNA per day for brain and 3.2x10(-9) per mtDNA per day
for liver. According to our model and in agreement with the
mitochondrial theory of aging, mtDNA mutations could cause the
detrimental changes seen in mitochondrial populations during the normal
lifespan of mice, while at the same time ensure that the mitochondrial
population remains functional during the developmental and reproductive
period of mice.
PMID: 16307857 [PubMed - as supplied by publisher]
