ArticleiScience2023
Age or lifestyle-induced accumulation of genotoxicity is associated with a length-dependent decrease in gene expression.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Tissue-Level Transcriptomic Entropy Reveals Organ-Specific Aging Patterns and Predicts Cancer Progression.Aging cell · 2026Article
- GARD: Genomic Data-Based Drug Repurposing in Head and Neck Cancer with Large Language Model Validation.Cancers · 2026Article
- GARD: Genomic Data based Drug Repurposing in Head and Neck Cancer with Large Language Model Validation.bioRxiv : the preprint server for biology · 2026Article
- Age Deceleration and Reversal Gene Patterns in Dauer Diapause.Aging cell · 2025Article
- RNA dysfunction in age-related macular degeneration: the role of U1 snRNP complex and neurodegenerative diseases.International journal of retina and vitreous · 2025Review
- Targeting DNA damage in ageing: towards supercharging DNA repair.Nature reviews. Drug discovery · 2025Review
- Transcriptional stress in aging: integrating experimental data and modeling to quantify DNA damage accumulation.Frontiers in molecular biosciences · 2025Article
- Improved health by combining dietary restriction and promoting muscle growth in DNA repair-deficient progeroid mice.Journal of cachexia, sarcopenia and muscle · 2024Article
- Gene length could be a critical factor in the aging of the genome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Aging clocks based on accumulating stochastic variation.Nature aging · 2024Article
- Evolutionary neurogenomics: Lengthy resolutions for complex brains.Current biology : CB · 2024Article
- Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain.Nucleic acids research · 2024Article
- DNA Damage and Parkinson's Disease.International journal of molecular sciences · 2024Review
- Time is ticking faster for long genes in aging.Trends in genetics : TIG · 2024Review
- Article
- Meta-Research: understudied genes are lost in a leaky pipeline between genome-wide assays and reporting of results.bioRxiv : the preprint server for biology · 2024Article
- The Road Less Traveled: Uncovering the Convergence Toward Specific Pleiotropic Phenotypes in Aging.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage has long been advocated as a molecular driver of aging. DNA damage occurs in a stochastic manner, and is therefore more likely to accumulate in longer genes. The length-dependent accumulation of transcription-blocking damage, unlike that of somatic mutations, should be reflected in gene expression datasets of aging. We analyzed gene expression as a function of gene length in several single-cell RNA sequencing datasets of mouse and human aging. We found a pervasive age-associated length-dependent underexpression of genes across species, tissues, and cell types. Furthermore, we observed length-dependent underexpression associated with UV-radiation and smoke exposure, and in progeroid diseases, Cockayne syndrome, and trichothiodystrophy. Finally, we studied published gene sets showing global age-related changes. Genes underexpressed with aging were significantly longer than overexpressed genes. These data highlight a previously undetected hallmark of aging and show that accumulation of genotoxicity in long genes could lead to reduced RNA polymerase II processivity.
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