Mouse and human transcriptome analysis links aging to genome-wide splicing degeneration
An integrative analysis of mouse and human tissue transcriptome data reports that aging is marked by a systematic decline in RNA splicing fidelity, termed splicing degeneration, which rose with age and was lower after calorie restriction or rapamycin treatment in the analyzed data. [1]
Automatic summary · not editorially reviewed
The key findings
An integrative analysis of mouse and human tissue transcriptome data reported that aging is characterized by systematic deterioration of RNA splicing fidelity, termed splicing degeneration. [1]
The level of splicing degeneration increased with age but was alleviated following calorie restriction or rapamycin treatment. [1]
Splicing degeneration was associated with age-associated changes in specific splicing factors, which in turn showed a strong association with age-related transcriptome changes. [1]
The source at a glance
- Study type / format
- Integrative transcriptome analysis (abstract)
- Population / context
- Mouse and human tissues analyzed in transcriptome datasets
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- June 29, 2026
Splicing degeneration across mouse and human tissues
The abstract describes an integrative analysis of transcriptome data from mouse and human tissues. The authors report that aging is characterized by systematic deterioration in the fidelity of RNA splicing, which they call splicing degeneration. They define it as a measure of functional alteration of the reading frame and domain configuration of protein products. Genes with higher aging-associated splicing degeneration were reported to be more conserved and enriched for processes such as RNA metabolism and antigen presentation.
Supporting source [1]
Level rose with age, lower after calorie restriction or rapamycin
By assessing alternative splicing events associated with functional deterioration, the authors quantified the degree of splicing degeneration. Its level increased with age but was alleviated following calorie restriction or rapamycin treatment, which the authors say indicates it can serve as a new molecular hallmark of aging. A meta-data analysis found splicing degeneration associated with age-associated changes in specific splicing factors, which in turn showed a strong association with age-related transcriptome changes.
Supporting source [1]
Abstract-only scope of the splicing degeneration findings
The abstract presents these as associations and describes splicing degeneration as a promising target for aging interventions acting to reverse it. It does not report sample sizes, follow-up, effect sizes or whether the calorie restriction and rapamycin observations came from interventions in the same datasets. The full text was not reviewed, so the methods and the strength of the evidence cannot be checked here.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Sample sizes, follow-up, effect sizes and the design behind the calorie restriction and rapamycin observations are not reported in the abstract. Findings are described as associations, not proven causes.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Zhang S, Tyshkovskiy A, Ying K, Wang S, Gladyshev VN. · europepmc.org · June 29, 2026