Research
Energy balance
Accumulation of mtDNA mutations in post-mitotic tissues (like muscle and brain) leads to tissue dysfunction via clonal expansion and mosaicity, rather than global oxidative damage levels.
Understand that aging in specific tissues (like muscle loss) is driven by localized cell failures, not just general 'oxidative stress'. This complexity explains why simple antioxidant interventions often fail to prevent age-related tissue decline.
GoodQualifiesHIGH confidence
High mosaicity and clonal expansion of mutated mtDNA provide a mechanism by which relatively low bulk tissue levels of mutant mtDNA can be causative for the age-dependent functional and structural decline... Mutant mtDNA, negatively affecting the ETC, could simply be lost from the tissue as affected cells die.
Why this rating
Strong evidence from single-cell studies in humans and animals showing clonal expansion and correlation with tissue dysfunction.
Source
The mitochondrial free radical theory of ageing - Where do we stand?
Jan Gruber · Frontiers in bioscience · 2008
DOI 10.2741/3174
narrative_reviewCited 168×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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