Clonal Expansion of Early to Mid-Life Mitochondrial DNA Point Mutations Drives Mitochondrial Dysfunction during Human Ageing

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Mitochondrial DNA (mtDNA) mutations have been shown to accumulate with age in a number of human stem cell populations and cause mitochondrial dysfunction within individual cells resulting in a cellular energy deficit. The dynamics by which mtDNA mutations occur and accumulate within individual cells (known as clonal expansion) is poorly understood. In particular we do not know when in the life-course these mtDNA mutations occur. Here we have measured mtDNA mutation frequency using three different techniques; Random Mutation Capture, which measures low level mutation frequency as an indirect measure of mutation rate, Next Generation Sequencing, which measures clonally expanded mtDNA mutation frequency, and mitochondrial enzyme histochemistry as a marker of clonally expanded mtDNA mutations, on colorectal mucosal biopsies obtained from 207 healthy participants aged 17–78 years. We show that, by 17 years of age, there is a substantial mtDNA point mutation burden and that clonal expansion of early to mid-life mtDNA mutations is likely to be the cause of mitochondrial dysfunction associated with ageing in the human colon.

Vyšlo v časopise: Clonal Expansion of Early to Mid-Life Mitochondrial DNA Point Mutations Drives Mitochondrial Dysfunction during Human Ageing. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004620
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004620

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