ArticleScientific reports2018
Comprehensive map of age-associated splicing changes across human tissues and their contributions to age-associated diseases.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 77 citations in OpenAlex.
- Alternative Splicing Constitutes a Transcription-independent Regulatory Layer in Replicative Senescence of Human Umbilical Cord Mesenchymal Stem Cells.Stem cell reviews and reports · 2026Article
- Novel RNA transcript signatures for accurate age prediction using RNA profiling.International journal of legal medicine · 2026Article
- Mammalian aging involves genome-wide splicing degeneration leading to functional decline.bioRxiv : the preprint server for biology · 2026Article
- Locus-specific LINE-1 mRNA expression reflects cell-type- and stimulus-specific senescence states.Nucleic acids research · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Dysregulation of alternative splicing patterns in the ovaries of reproductively aged mice.Reproduction (Cambridge, England) · 2026Article
- Antisense Oligonucleotide Therapeutics Targeting Age-Related Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- The implications of alternative splicing regulation for maximum lifespan.Nature communications · 2025Article
- Unveiling proteomic and peptide-level modifications in cerebrospinal fluid and plasma in normal cognitive aging.Communications medicine · 2025Article
- Article
- Transcript diversity in aging: cryptic transcription and splicing.Medical review (2021) · 2025Review
- mRNA Isoforms and Variants in Health and Disease.International journal of molecular sciences · 2025Review
- The Implications of Alternative Splicing Regulation for Maximum Lifespan.bioRxiv : the preprint server for biology · 2025Article
- Splicing accuracy varies across human introns, tissues, age and disease.Nature communications · 2025Article
- mRNA Transcript Variants Expressed in Mammalian Cells.International journal of molecular sciences · 2025Review
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- Progerin mRNA expression in non-HGPS patients is correlated with widespread shifts in transcript isoforms.NAR genomics and bioinformatics · 2024Article
- TREM2 variants that cause early dementia and increase Alzheimer's disease risk affect gene splicing.Brain : a journal of neurology · 2024Article
- Article
- Noncoding RNA Contribution to Aging and Lifespan.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
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Abstract
Alternative splicing contributes to phenotypic diversity at multiple biological scales, and its dysregulation is implicated in both ageing and age-associated diseases in human. Cross-tissue variability in splicing further complicates its links to age-associated phenotypes and elucidating these links requires a comprehensive map of age-associated splicing changes across multiple tissues. Here, we generate such a map by analyzing ~8500 RNA-seq samples across 48 tissues in 544 individuals. Employing a stringent model controlling for multiple confounders, we identify 49,869 tissue-specific age-associated splicing events of 7 distinct types. We find that genome-wide splicing profile is a better predictor of biological age than the gene and transcript expression profiles, and furthermore, age-associated splicing provides additional independent contribution to age-associated complex diseases. We show that the age-associated splicing changes may be explained, in part, by concomitant age-associated changes of the upstream splicing factors. Finally, we show that our splicing-based model of age can successfully predict the relative ages of cells in 8 of the 10 paired longitudinal data as well as in 2 sets of cell passage data. Our study presents the first systematic investigation of age-associated splicing changes across tissues, and further strengthening the links between age-associated splicing and age-associated diseases.
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