Cell and rat experiments link ZNF865 with disc cell damage and senescence, but they don’t show that changing the gene can treat back pain in people.
A gene called ZNF865 may help protect the cells that maintain spinal discs from age-related damage, according to research published in Aging Cell. In human cells, increasing the gene’s activity reduced several signs of cellular aging and damage. In rats, switching off a related gene in disc cells led to changes associated with degeneration and increased pain sensitivity. These early findings point to a possible biological role for ZNF865, but they don’t establish a treatment for back pain or disc disease.
Why researchers looked at ZNF865
Intervertebral discs cushion the bones of the spine. Their central region, the nucleus pulposus, contains cells that help maintain the surrounding tissue. With age and disc degeneration, these cells can enter a senescent state: they stop dividing and release inflammatory signals, often grouped under the name senescence-associated secretory phenotype, or SASP. Those signals can affect nearby cells and contribute to changes in the extracellular matrix, the material that supports disc tissue.
Earlier research has found senescent cells in aging and deteriorating discs in both people and animals. Animal studies have also explored senolytic drugs, which aim to remove senescent cells. For example, one study reported less age-related disc degeneration in older mice given dasatinib and quercetin. That result is from mice; it does not show that the combination treats people’s back pain.
The researchers behind the new study had previously used CRISPR gene editing in engineered disc cells and found that ZNF865 was linked with cartilage production, tissue maturation and mechanical properties. Their earlier gene expression work also connected ZNF865 with senescence. They therefore set out to examine whether the gene might influence disc cell aging and damage.
Findings in human cells
The team analyzed gene activity in three cell types: human nucleus pulposus cells from degenerating discs, fat-derived cells and HEK293 cells, a widely used laboratory cell line. Across these groups, ZNF865 was associated with processes involving cell replication, DNA repair, the mTOR pathway and senescence. These associations helped guide the experiments, but by themselves do not establish how the gene acts.
In samples from people with lower back pain and from trauma patients, ZNF865 levels were lower in degenerative nucleus pulposus cells than in cells from healthy discs. The researchers also found that levels declined with age in healthy disc cells. They reported a similar age-related pattern in mice examined at 4, 12 and 24 months. Cells from degenerating human discs also showed more markers of DNA damage than cells from healthy discs.
To test the gene’s role, the researchers used CRISPR to silence ZNF865 in healthy human disc cells. Compared with unsilenced cells, the edited cells had roughly five times as many markers of senescence, alongside a significant rise in DNA damage markers. This suggests that reducing the gene’s activity can affect these features in a lab setting; it doesn’t show what would happen in a person.
In a separate experiment, the team increased ZNF865 activity in cells from degenerating discs. Those cells multiplied faster, and several senescence markers fell to levels close to those seen in healthy cells. The researchers also measured lower SASP activity and inflammation, less DNA damage, and higher collagen expression. Collagen is part of the extracellular matrix, so the change may indicate improved support for disc tissue. These results remain laboratory findings.
Rat experiment and evidence limits
The team also examined chromatin, the DNA and proteins that shape how genes are accessed. After ZNF865 was increased in degenerative disc cells, their chromatin accessibility more closely resembled that of healthy cells. The researchers reported a 94% reduction in the differences they measured between the two groups and found no pathways upregulated relative to healthy cells. A separate analysis of gene expression also pointed toward a healthier overall pattern.
For the animal experiment, the researchers used a CRISPR vector to silence the rat counterpart of ZNF865 in nucleus pulposus cells, then injected those cells into the animals’ vertebral discs. In less than two months, the rats developed signs associated with disc degeneration, including greater sensitivity to pain. Their disc tissue also showed increased senescence, SASP proteins and genetic damage. This experiment tested the effects of reducing the gene’s activity; it did not test whether raising ZNF865 could reverse degeneration or relieve pain in living animals.
The findings are promising as a lead for further research, but the study has important limits. The human cell work used samples from a limited number of people, and the rat experiment focused on gene silencing. The researchers have not yet established the molecular steps through which ZNF865 may produce its effects. They also reported that no antibodies, inhibitors or activators are currently available to directly change the gene’s activity in cells; their experiments relied on CRISPR.
Before ZNF865 could be considered as a possible treatment, researchers would need a practical way to affect it and evidence from animal studies showing that this approach can reduce disc degeneration or related effects in living organisms. The current results don’t establish whether it can prevent or treat back pain in people. For readers managing persistent back symptoms or questions about disc health, a doctor or pharmacist can help discuss their circumstances and available care.
