ArticleeLife2023
The multi-tissue landscape of somatic mtDNA mutations indicates tissue-specific accumulation and removal in aging.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- Variations in mitochondrial genome as potential prognostic markers in sickle cell disease.Haematologica · 2026Article
- Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response and promote progressive heart failure.Science advances · 2026Article
- Mitochondrial molecular diversity in the brain.Current opinion in neurobiology · 2026Review
- Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Mitochondrial genetic variation across tissues of the human body.Nucleic acids research · 2026Article
- Accumulated mtDNA mutations are linked to specific impairments in NADH-linked respiration.iScience · 2026Article
- Single-cell multi-omic analysis of mitochondrial mutational mosaicism and dynamics.Nature communications · 2026Article
- Immune Cell Mitochondrial Phenotypes Are Largely Preserved in Mitochondrial Diseases and Do Not Reflect Disease Severity.Neurology. Genetics · 2026Article
- Cellular heterogeneity and therapeutic response profiling of human IDH + glioma stem cell cultures.Scientific reports · 2025Article
- Clonal cell states link gastroesophageal junction tissues with metaplasia and cancer.Nature communications · 2025Article
- Evaluating Selective Quality Control in Mammalian Oogenesis: Evidence and Opportunities.Annual review of genetics · 2025Review
- Reversible compromise of physiological resilience by accumulation of heteroplasmic mtDNA mutations.Science (New York, N.Y.) · 2025Article
- Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations.Science advances · 2025Article
- Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review).International journal of molecular medicine · 2025Review
- Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging.Nature aging · 2025Article
- Sequencing and characterizing human mitochondrial genomes in the biobank-based genomic research paradigm.Science China. Life sciences · 2025Review
- Endometrial Aging and Reproductive Decline: The Central Role of Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- Tapping natures rhythm: the role of season in mitochondrial function and genetics in the UK biobank.Human genomics · 2025Article
- Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances.Signal transduction and targeted therapy · 2025Review
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14 authors at 1 institution in 1 country.
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Abstract
Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism of mitochondrial and tissue dysfunction that occurs during aging. A thorough characterization of age-associated mtDNA somatic mutations has been hampered by the limited ability to detect low-frequency mutations. Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect >89,000 independent somatic mtDNA mutations and show significant tissue-specific increases during aging across all tissues examined which did not correlate with mitochondrial content and tissue function. G→A/C→T substitutions, indicative of replication errors and/or cytidine deamination, were the predominant mutation type across all tissues and increased with age, whereas G→T/C→A substitutions, indicative of oxidative damage, were the second most common mutation type, but did not increase with age regardless of tissue. We also show that clonal expansions of mtDNA mutations with age is tissue- and mutation type-dependent. Unexpectedly, mutations associated with oxidative damage rarely formed clones in any tissue and were significantly reduced in the hearts and kidneys of aged mice treated at late age with elamipretide or nicotinamide mononucleotide. Thus, the lack of accumulation of oxidative damage-linked mutations with age suggests a life-long dynamic clearance of either the oxidative lesions or mtDNA genomes harboring oxidative damage.
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