Omics · study · 2026
LIVER EXERCISE FACTOR REVERSES AGING AND ALZHEIMER’S-RELATED MEMORY LOSS BY TARGETING BRAIN VASCULATURE
Listed in NCBI GEO
Blood factors transfer the benefits of exercise to the aged brain.
Description
However, mechanisms to restore cognition and the translational application to neurodegenerative disorders are unknown. Here we show that liver-derived exercise factor glycosylphosphatidylinositol (GPI)-specific phospholipase D1(Gpld1)–a GPI-degrading enzyme–reverses aging and Alzheimer’s-related memory loss by targeting brain vasculature.
Increasing Gpld1 rejuvenated transcriptional hippocampal aging signatures at a single cell level and rescued memory in aged mice. Mechanistically, we identified GPI-anchored tissue-nonspecific alkaline phosphatase (TNAP) on brain vasculature as a GPLD1 substrate. Mimicking an age-related increase in cerebrovascular TNAP impaired memory in young mice and mitigated Gpld1-mediated cognitive benefits in aged mice.
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Inhibiting TNAP activity recapitulated the benefits of Gpld1 in old age. In an Alzheimer’s disease model, increasing Gpld1, or inhibiting TNAP, ameliorated A pathology and improved cognitive deficits. Collectively, our data identify cerebrovasculature as a gatekeeper of the restorative cognitive benefits of a liver-to-brain exercise axis.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE269nnn/GSE269061 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269061 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1120039 ncbi.nlm.nih.gov/bioproject/PRJNA1120039 ↗
project · from NCBI GEO
- PubMed 41713415 pubmed.ncbi.nlm.nih.gov/41713415 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE269061 | 14 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:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | 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 |