Omics · study · 2026
Developmental programming of late-life proteostasis and longevity by NuA4 complex activity in early life [CUT&Tag]
Listed in NCBI GEO
Maintaining proteostasis is essential for healthy aging and preventing neurodegenerative diseases like Alzheimer's disease, yet its collapse in late life leads to irreversible pathologies.
Description
It is unknown if there exists an early-life window where proteostasis can be programmed to confer lasting resilience, offering a preventative approach against these conditions. Leveraging short life cycle and the genetical tractability of Caenorhabditis elegans, we discover that inhibition of the TIP60/NuA4 acetyltransferase complex in early life can enhances late-life proteostasis and extends lifespan.
We found that reducing early-life NuA4 activity diminishes epigenetic priming of H4K16ac, triggering compensatory activation of the XBP-1-mediated unfolded protein response (UPRER). This early-life-predominant XBP-1 activation remodels ER structure and reprograms lipid metabolism. Crucially, early-life NuA4/H4K16ac suppression boost oleic acid accumulation, which confers late-life health benefits.
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Overall, our study demonstrates the principle of developmental plasticity in shaping late-life proteostasis and reveals the potential for early interventions to combat neurodegeneration and aging.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300494 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300494 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1281068 ncbi.nlm.nih.gov/bioproject/PRJNA1281068 ↗
project · from NCBI GEO
Topics
- Stated by source
- Caenorhabditis elegans · Genome binding/occupancy profiling by high throughput sequencing
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE300494 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| 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 |