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Mammalian aging involves genome-wide splicing degeneration leading to functional decline
Biorxiv : the Preprint Server for Biology
|July 10, 2026
Summary
Aging leads to "splicing degeneration," a decline in RNA splicing fidelity impacting protein products. This molecular hallmark of aging can be reversed by interventions like calorie restriction.
Area of Science:
- Molecular Biology
- Genetics
- Aging Research
Background:
- Alternative splicing changes significantly during development and aging.
- The functional consequences of age-associated splicing dysregulation are not well understood.
Purpose of the Study:
- To investigate the link between aging, RNA splicing fidelity, and functional outcomes.
- To identify splicing degeneration as a molecular hallmark of aging and a potential target for interventions.
Main Methods:
- Integrative analysis of transcriptome data from mouse and human tissues.
- Quantification of splicing degeneration by assessing age-associated alternative splicing events.
- Meta-data analysis to explore the relationship between splicing degeneration and splicing factors.
Main Results:
- Aging is characterized by systematic "splicing degeneration," affecting protein products.
- Genes with higher splicing degeneration are conserved and involved in RNA metabolism and antigen presentation.
- Splicing degeneration increases with age but is alleviated by calorie restriction or rapamycin treatment.
- Splicing degeneration is linked to age-associated changes in splicing factors and transcriptome alterations.
Conclusions:
- Splicing degeneration serves as a novel molecular hallmark of aging.
- Interventions targeting splicing degeneration may offer therapeutic benefits for aging.
- The study reveals a strong association between aging and genome-wide splicing degeneration.
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