What this means
Researchers found ZNF865 levels drop with age and disc disease, and changing it affected aging signs in cells. Mouse results suggest it may matter for disc damage and pain, but this does not show it works as a treatment.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Human and mouse disc samples, human disc cells in a lab, and mice
- Kind of research
- A study
The science
- Original title
- ZNF865 (BLST) a Novel Regulator of DNA Damage and Cell Senescence in Back Pain.
- Authors
- Lewis C, Levis H, Holbrook J et al.
- Journal
- Aging cell
- Published
- Oct 10, 2026
- Study type
- Study · in humans
- PMID
- 42855835 ↗
Abstract
Senescence has been shown to contribute to the progression of aging-related diseases including degenerative disc disease (DDD). However, the mechanisms regulating senescence in the intervertebral disc (IVD) and other tissues/diseases remain poorly understood. Recently, ZNF865 (BLST) was identified as a previously uncharacterized zinc finger protein that regulates a wide array of genes related to protein processing, cell senescence, and DNA damage repair. Here, we show that ZNF865 expression decreases with age and pathology in human and mouse IVD samples. Utilizing CRISPR-guided gene modulation, we show that ZNF865 is necessary for healthy cell function and is a critical protein in regulating senescence and DNA damage in IVD cells, with implications for a wide range of tissues and organs. We also demonstrate that downregulation of ZNF865 induces senescence in asymptomatic human nucleus pulposus (NP) cells. Conversely, restoration in degenerative NP cells mitigates senescence, SASP expression, and DNA damage, enhances ECM anabolism, and restores chromatin accessibility and gene expression to a healthy state. In vivo, CRISPRi of ZNF865 induces disc degeneration and painful behaviors. Collectively, our findings establish ZNF865 as a novel regulator of genome stability and a potential therapeutic target for mediating senescence/DNA damage in aging related diseases.
Lewis C, Levis H, Holbrook J et al. ZNF865 (BLST) a Novel Regulator of DNA Damage and Cell Senescence in Back Pain. Aging cell. 2026. doi:10.1111/acel.70754. PMID: 42855835. https://pubmed.ncbi.nlm.nih.gov/42855835/