ArticleProceedings of the National Academy of Sciences of the United States of America2022
Advanced age increases frequencies of de novo mitochondrial mutations in macaque oocytes and somatic tissues.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Inheritance and selection of the mitochondrial genome.Nature reviews. Genetics · 2026Review
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
- Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.Archives of toxicology · 2026Review
- Mitochondrial genetic variation across tissues of the human body.Nucleic acids research · 2026Article
- Mammalian mitochondrial DNA accumulates insertions and deletions with age in energetically demanding tissues.Molecular biology and evolution · 2026Article
- De novo rates of aProceedings of the National Academy of Sciences of the United States of America · 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
- Selfish mutations promote age-associated erosion of mtDNA integrity in mammals.Nature communications · 2025Article
- Sequencing and characterizing human mitochondrial genomes in the biobank-based genomic research paradigm.Science China. Life sciences · 2025Review
- Mitochondrial DNA Damage and Its Repair Mechanisms in Aging Oocytes.International journal of molecular sciences · 2024Review
- Maintaining mitochondrial DNA copy number mitigates ROS-induced oocyte decline and female reproductive aging.Communications biology · 2024Article
- Young small extracellular vesicles rejuvenate replicative senescence by remodeling Drp1 translocation-mediated mitochondrial dynamics.Journal of nanobiotechnology · 2024Article
- Maternal age enhances purifying selection on pathogenic mutations in complex I genes of mammalian mtDNA.Nature aging · 2024Article
- Ovarian aging: energy metabolism of oocytes.Journal of ovarian research · 2024Review
- AMPK Suppression Due to Obesity Drives Oocyte mtDNA Heteroplasmy via ATF5-POLG Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout ageing.Nature ecology & evolution · 2024Article
- In vivo imaging of mitochondrial DNA mutations using an integrated nano Cas12a sensor.Nature communications · 2023Article
- Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout aging.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 4 countries.
Funding
Abstract
Mutations in mitochondrial DNA (mtDNA) contribute to multiple diseases. However, how new mtDNA mutations arise and accumulate with age remains understudied because of the high error rates of current sequencing technologies. Duplex sequencing reduces error rates by several orders of magnitude via independently tagging and analyzing each of the two template DNA strands. Here, using duplex sequencing, we obtained high-quality mtDNA sequences for somatic tissues (liver and skeletal muscle) and single oocytes of 30 unrelated rhesus macaques, from 1 to 23 y of age. Sequencing single oocytes minimized effects of natural selection on germline mutations. In total, we identified 17,637 tissue-specific de novo mutations. Their frequency increased ∼3.5-fold in liver and ∼2.8-fold in muscle over the ∼20 y assessed. Mutation frequency in oocytes increased ∼2.5-fold until the age of 9 y, but did not increase after that, suggesting that oocytes of older animals maintain the quality of their mtDNA. We found the light-strand origin of replication (OriL) to be a hotspot for mutation accumulation with aging in liver. Indeed, the 33-nucleotide-long OriL harbored 12 variant hotspots, 10 of which likely disrupt its hairpin structure and affect replication efficiency. Moreover, in somatic tissues, protein-coding variants were subject to positive selection (potentially mitigating toxic effects of mitochondrial activity), the strength of which increased with the number of macaques harboring variants. Our work illuminates the origins and accumulation of somatic and germline mtDNA mutations with aging in primates and has implications for delayed reproduction in modern human societies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.