Back to Search
Start Over
Comprehensive map of age-associated splicing changes across human tissues and their contributions to age-associated diseases
- Source :
- Scientific Reports, Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
- Publication Year :
- 2017
-
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.
- Subjects :
- 0301 basic medicine
Male
Aging
Longitudinal data
Biological age
RNA Splicing
lcsh:Medicine
Computational biology
Biology
Article
03 medical and health sciences
Humans
Genetic Predisposition to Disease
lcsh:Science
Gene
Gene transcript
Multidisciplinary
Sequence Analysis, RNA
Gene Expression Profiling
lcsh:R
Alternative splicing
Phenotype
Alternative Splicing
030104 developmental biology
Organ Specificity
RNA splicing
RNA
lcsh:Q
Female
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....f311f7a9ed276e435d65316ff50cc1f1