ArticlePLoS genetics2014
Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 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
97 citing papers in PubMed, 172 citations in OpenAlex.
- Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts.EBioMedicine · 2018Trial
- Mitochondrial dysfunction and inflammaging: a mechanistic bridge between bioenergetic failure and senescence.GeroScience · 2026Review
- Temporal control of mitochondrial mutagenesis reveals the fate of mtDNA mutations with age.bioRxiv : the preprint server for biology · 2026Article
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
- Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response and promote progressive heart failure.Science advances · 2026Article
- Review
- Article
- Mitochondrial transfer technologies with molecular insights into clinical applications.Stem cells (Dayton, Ohio) · 2026Review
- Mammalian mitochondrial DNA accumulates insertions and deletions with age in energetically demanding tissues.Molecular biology and evolution · 2026Article
- Nanoparticle-Based Tools to Study Hallmarks of Aging at the Molecular Level.International journal of nanomedicine · 2026Review
- Age-related hearing loss involves mitochondrial DNA instability and copy number depletion in the cochlea: Insights from in vivo and in vitro models.Hearing research · 2026Article
- The microRNA miR-71 suppresses maladaptive UPRNature communications · 2025Article
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- HMGB1 and mitochondrial dysfunction: a double-edged sword in ageing.Open biology · 2025Review
- Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging.Nature aging · 2025Article
- Metabolic dysfunction promoted by mitochondrial DNA mutation burden drives retinal degeneration.bioRxiv : the preprint server for biology · 2025Article
- Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments.Clinical and translational medicine · 2025Review
- Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Targeting the Electron Transport System for Enhanced Longevity.Biomolecules · 2025Review
- Cryptic mitochondrial DNA mutations coincide with mid-late life and are pathophysiologically informative in single cells across tissues and species.Nature communications · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium.
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.