Mechanism of age-related accumulation of mtDNA mutations in human blood - PubMed
2 hours ago
- #clonal haematopoiesis
- #mtDNA mutations
- #ageing biomarkers
- Mitochondrial DNA (mtDNA) mutations accumulate sharply around age 60 in human blood, primarily as low-level heteroplasmic single-nucleotide variants (mtSNVs).
- The mutation spectrum suggests these are likely neutral and result from replication errors, not oxidative damage as previously thought.
- Genetic associations link high mtSNV burden to germline variants near TERT, TCL1A, and SMC4, and to mutations in clonal haematopoiesis (CH) driver genes, even without known CH mutations.
- MtDNA mutations become detectable with age due to cellular clone expansion from clonal haematopoiesis, making mtDNA a sensitive marker for somatic mosaicism.
- The findings unify three ageing signatures: common TERT variants, clonal haematopoiesis, and mtDNA mutation accumulation.