ArticleNature genetics2023
Genome-wide RNA polymerase stalling shapes the transcriptome during aging.
Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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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.
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Who cites it
84 citing papers in PubMed, 131 citations in OpenAlex.
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
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- Nuclear class 3 PI3K co-activates fasting-specific chromatin remodelling.Nature cell biology · 2026Article
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- Consistent changes in global gene expression patterns despite strong variation in individual gene expression in the male mouse hippocampus following early life stress.Neurobiology of stress · 2026Article
- Nuclear export of R-loop by the DDX1 and XPO1 complex promotes senescence-associated secretory phenotype and inflammaging.Nature aging · 2026Article
- Resolving Sub-Nuclear Architecture from Compartments to Functional Domains.International journal of molecular sciences · 2026Review
- Telomere Dysfunction and Proteostasis Decline Define Distinct Pathways of Cellular Senescence in the Human Respiratory Tract.Aging cell · 2026Article
- Native entanglement misfolding contributes to age-associated structural changebioRxiv : the preprint server for biology · 2026Article
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- Aging clocks delineate neuron types vulnerable or resilient to neurodegeneration and identify neuroprotective interventions.Nature aging · 2026Article
- Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease.Nature reviews. Molecular cell biology · 2026Review
- Single-cell transcriptomics reveal intrinsic and systemic T cell aging in COVID-19 and HIV.Aging · 2026Article
- The expanding roles of homologous recombination proteins in genome stability.The EMBO journal · 2026Review
- Superenhancers shape the landscape and repair dynamics of transcription-associated DNA breaks in cancer.Science advances · 2026Article
- Review
- The Use of Nutritional Interventions to Enhance Genomic Stability in Mice and Delay Aging.Nutrients · 2026Review
- Of Barriers and Loops-How Evolution Limits Most Cancer Risks to Older Ages.Cancer discovery · 2026Review
- Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulators.Science advances · 2026Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Gene expression profiling has identified numerous processes altered in aging, but how these changes arise is largely unknown. Here we combined nascent RNA sequencing and RNA polymerase II chromatin immunoprecipitation followed by sequencing to elucidate the underlying mechanisms triggering gene expression changes in wild-type aged mice. We found that in 2-year-old liver, 40% of elongating RNA polymerases are stalled, lowering productive transcription and skewing transcriptional output in a gene-length-dependent fashion. We demonstrate that this transcriptional stress is caused by endogenous DNA damage and explains the majority of gene expression changes in aging in most mainly postmitotic organs, specifically affecting aging hallmark pathways such as nutrient sensing, autophagy, proteostasis, energy metabolism, immune function and cellular stress resilience. Age-related transcriptional stress is evolutionary conserved from nematodes to humans. Thus, accumulation of stochastic endogenous DNA damage during aging deteriorates basal transcription, which establishes the age-related transcriptome and causes dysfunction of key aging hallmark pathways, disclosing how DNA damage functionally underlies major aspects of normal aging.
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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.