Targeting aging cells could slow disc degeneration

Neck and low back pain affect millions worldwide and is a top factor of living with disability. Degeneration of the discs that cushion the spine is a leading cause. Current treatments can relieve symptoms but do little to slow the underlying disease. Now, researchers from Thomas Jefferson University have shown that targeting harmful, aging cells early may preserve disc health and delay degeneration.

The study, published in Bone Research, focused on cellular senescence, a state in which cells become dormant but still release inflammatory molecules that can damage surrounding tissue. While senescence is a hallmark of aging, the researchers wanted to determine whether it also contributes to disc degeneration that begins earlier in life.

The team found that the cells in spinal discs of young mice with early-onset degeneration looked like the senescent cells of much older mice. The findings indicated that there may be an opportunity to intervene before the disease sets in.

“This study demonstrates for the first time in animals that cell senescence may play a pathological role in early onset disc degeneration,” says cell biologist and senior author of the study, Makarand Risbud.

The researchers then tested a combination of the drugs dasatinib and quercetin (DQ) to target senescent cells. They found mice treated with DQ had healthier discs, lower levels of inflammation and tissue scarring, and more of the specialized cells needed to maintain healthy spinal discs.

To better understand why the combination drug worked, the researchers analyzed gene activity in the discs. They found that DQ reduced activity in genes linked to inflammation, cell death and cellular aging. The results also identified a signaling pathway known as JUN as a potential driver of degeneration. Blocking JUN activity in human disc cells reproduced many of the protective effects seen with DQ treatment.

Together, the findings suggest that removing senescent cells early may help slow disc degeneration before irreversible damage occurs.

“We are excited by these findings,” says Dr. Risbud. Because dasatinib and quercetin have already been studied in people for other age-related conditions, the approach could eventually be explored as a treatment for disc-related low back pain.

By Roni Dengler