Excel · study · 2026
Adulthood depletion of Integrator extends lifespan and healthspan via defective pre-mRNA processing [RNA-seq]
Listed in NCBI GEO
Identifying strategies to mitigate age-related physiological decline remains a central challenge.
Description
Transcriptional regulation is essential to organismal healthspan and a frequent therapeutic target in ageing research. The Integrator complex is a highly conserved regulator of transcriptional quality control and RNA processing, yet its role in ageing within an intact organism remains unknown.
Using adult-specific RNAi in Caenorhabditis elegans, we find that depletion of most Integrator subunits extends lifespan and healthspan. Mechanistically, loss of the catalytic subunit INTS11 disrupts 3′ end formation of small nuclear and spliced-leader RNAs, impairing trans-splicing and promoting outron retention on a subset of transcripts enriched for spliceosomal, nucleocytoplasmic import and mitochondrial functions.
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These RNA-processing defects engage endogenous siRNA pathways, which are required for the longevity and healthspan benefits of INTS11 depletion, consistent with a role in buffering the cytoplasmic burden of misprocessed splicing and import factors. In parallel, outron retention compromises nuclear-encoded mitochondrial gene expression and induces a hormetic decline in mitochondrial function. Together, our findings identify Integrator as an upstream regulator of a coupled RNA-processing–small RNA–mitochondrial axis that shapes the pace of ageing.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325594 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325594 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1440521 ncbi.nlm.nih.gov/bioproject/PRJNA1440521 ↗
project · from NCBI GEO
Topics
- Stated by source
- Caenorhabditis elegans · Expression profiling by high throughput sequencing
- From keywords
- Life Sciences
- Inferred from text
- Genetics 68% · RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE325594 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].anzsrc:group:3105 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (68%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:6239 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |