Mitochondrial DNA Damage and Stem Cell Aging
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Mitochondrial DNA damage is theorized, with a great deal of evidence in support, to be one of the causes of degenerative aging. This research is somewhat relevant, but the focus on point mutations is problematic: there is other research in mice to demonstrate that point mutations in mitochondrial DNA are not all that important. The important types of damage are more severe, such as deletions in which stretches of DNA are simply dropped. The mice used here do in fact have an increased number of deletions, even though that isn't mentioned in the abstract below, so be careful of claims of associations of dysfunction with point mutations.

A decline in the replicative and regenerative capacity of adult stem cell populations is a major contributor to the ageing process. Mitochondrial DNA (mtDNA) mutations clonally expand with age in human stem cell compartments including the colon, small intestine and stomach and result in respiratory chain deficiency. Studies in a mouse model with high levels of mtDNA mutations due to a defect in the proof-reading domain of the mtDNA polymerase γ (mtDNA mutator mice) have established causal relationships between the accumulation of mtDNA point mutations, stem cell dysfunction and premature ageing.

These mtDNA mutator mice have also highlighted that the consequences of mtDNA mutations upon stem cells vary depending on the tissue. In this review we present evidence that these studies in mice are relevant to normal human stem cell ageing and we explore different hypotheses to explain the tissue specific consequences of mtDNA mutations. In addition, we emphasize the need for a comprehensive analysis of mtDNA mutations and their effects on cellular function in different ageing human stem cell populations.


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