Omics · study · 2026
Small-molecule targeting of KIF2C enhances double-strand break DNA repair and slows down aging
Listed in NCBI GEO
DNA damage is a central driver of the aging process.
Description
We previously found that the kinesin-13 KIF2C, shown to play a role in DNA repair, is repressed in aged cells. Here, we investigated whether increased KIF2C activity can counteract DNA damage and its impact on aging-related phenotypes.
We demonstrate that a small-molecule agonist of KIF2C enhances DNA repair in two distinct genetic disorders characterized by pervasive DNA damage and accelerated aging: the Hutchinson-Gilford progeria syndrome (HGPS) and the Down syndrome (DS). Mechanistically, KIF2C agonist improves the repair of DNA double-strand breaks (DSBs) in patient-derived cells by reinstating the assembly of nuclear envelope invaginations driven by cytoplasmic microtubules.
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Enhanced DSB DNA repair in HGPS and DS cells translated into amended nuclear structure and transcriptional signatures. Moreover, subcutaneous administration of the KIF2C agonist in progeria mice mitigated aging phenotypes and extended both health and lifespan. Our study discloses a novel geroprotective pharmacological approach that acts by hindering DSB DNA damage, and thus we unprecedentedly demonstrate that enhanced genome stability can delay aging.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE321nnn/GSE321805 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE321805 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1429339 ncbi.nlm.nih.gov/bioproject/PRJNA1429339 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE321805 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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[organism].NCBITaxon:9606 | 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 |