Omics · study · 2026
Epigenetic Activation of SIRT6 Protects the Aging Intervertebral Disc
Listed in NCBI GEO
Aging is one of the important risk factors for Intervertebral disc degeneration, a major contributor to chronic low back and neck pain.
Description
Our recent work has demonstrated a promising role for SIRT6, a nuclear NAD⁺- dependent deacetylase and defatty acylase, in maintaining intervertebral disc health with aging. We therefore investigated whether SIRT6 activation improves outcomes of disc health by studying the spinal phenotype of 24-month-old mice treated with a well-studied agonist, MDL-800, for 6 months.
Histological studies revealed healthy disc tissue morphology, enhanced cell viability, and lower degeneration scores in mice treated with MDL-800. Further mechanistic insights revealed that SIRT6 activation decreased H3K9ac levels, improved cell phenotype and matrix quality, and reduced the SASP burden in the disc, characterized by decreased abundance of p21, IL-6 and TGF-b. Tissue RNA-Seq, in vitro measurements of histone 3 modifications, and multi-omics ATAC-seq/RNA-seq analyses revealed that SIRT6 activation altered the epigenetic status (decreased H3K9ac, H3K36me3, and H3K79me2) and transcriptomic landscape of disc cells.
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Notably, MDL-800 treatment increased LC3II levels, indicating enhanced autophagic flux in nucleus pulposus cells. Furthermore, plasma LC-MS and NMR analyses revealed minimal systemic metabolic changes. ScRNA sequencing of splenocytes and bone marrow cells showed a decrease in the proportions of B cells, T cells, and granulocytes, without an altered systemic cytokine profile, indicating good tolerance and the absence of systemic inflammation following MDL-800 treatment.
Our study demonstrates that SIRT6 activation modulates autophagy and cell senescence in the disc, underscoring the feasibility of targeting SIRT6 activation as a promising pharmacological strategy to maintain disc health in the aging spine.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320197 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320197 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1427130 ncbi.nlm.nih.gov/bioproject/PRJNA1427130 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Mass spectrometry 65% · RNA sequencing 65% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE320197 | 12 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[modality].local:modality:mass-spectrometry | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |