• Dasatinib and Quercetin target aged, non-proliferating cells
  • Treating mice with these two drugs mitigates age-related spinal disc degeneration
  • If these results translate to humans, Dasatinib and Quercetin could provide a means to alleviate age-related lower back pain

Many people experience lower back pain as they age, and the few clinical interventions that do exist like surgery temporarily relieve symptoms with suboptimal results. The root of age-related lower back pain comes from the accumulation of aged, non-proliferating cells called senescent cells, which current therapeutic options don’t necessarily address.

Risbud and colleagues from Thomas Jefferson University published an in-review study in Research Square describing how administering mice two drugs that target senescent cells mitigated age-dependent intervertebral disc degeneration. They found the senolytic drugs Dasatinib and Quercetin provide beneficial effects ameliorating aged back problems when drug administration began earlier but not later in life. If these results translate to humans, it means Dasatinib and Quercetin administered during a therapeutic time window could improve age-related lower back pain and associated symptoms.

“Our results show for the first time that [Dasatinib and Quercetin] combination could target senescence in the mouse disc, and these results provide proof of principle that senolytics may be useful in mitigating age-dependent disc degeneration,” concluded the research team from Thomas Jefferson University regarding the Dasatinib and Quercetin-induced improvements seen in aged intervertebral discs.

Dasatinib and Quercetin Treatment Preserves Intervertebral Disc Tissue Architecture and Reduces Cell Death

To take a closer look at the effects of Dasatinib and Quercetin treatment in aged mice, Risbud and colleagues examined aged mouse intervertebral disc degeneration and senescent cell presence following weekly 5 mg/kg Dasatinib and 50 mg/kg Quercetin injections. They found that mice treated from 6 to 23 months and 14 to 23 months had improved tissue and cell integrity preservation but that those treated from 18 to 23 months did not. The team of researchers also evaluated several aged, non-proliferating senescent cell markers and found Dasatinib and Quercetin treatment reduced them. Altogether, their results suggest that Dasatinib and Quercetin treatment mitigates aged mouse disc degeneration and reduces intervertebral disc senescent cell numbers.

(Risbud et al., 2021 | Research Square) Dasatinib and Quercetin treatment from ages 14 to 23 months preserves tissue architecture and cell integrity. The left column shows the tissue architecture of 23-month-old mice without Dasatinib and Quercetin treatment, and the right column shows it after administering the two drugs. Cells called chondrocytes in each cell layer have more defined boundaries with Dasatinib and Quercetin treatment. The cells produce a matrix of collagen with proteins called proteoglycans stained red. In aged tissue, proteoglycans accumulate as the red stain in the image indicates. With Dasatinib and Quercetin treatments, proteoglycan concentrations diminish indicative of greater tissue health. Disc = intervertebral disc; NP = nucleus puposus, a tissue without blood vessels; AF = annulus fibrous, a cell layer composed of the structural component of connective tissues called collagen; CEP = cartilaginous endplates, an area bordering the NP and AF in the bone of the skull called the cranium.

(Risbud et al., 2021 | Research Square) Dasatinib and Quercetin treatment from 14 to 23 months of age diminished the dead or dying intervertebral disc cells. One-year-old healthy mice show few dead or dying, TUNEL-stained (red) intervertebral disc cells (F). Twenty-three-month-old mice not given Dasatinib and Quercetin show marked elevations in dead or dying, TUNEL-stained cells (F’) with arrows pointing to three clusters of them. Treatment with Dasatinib and Quercetin from 14 to 23 months of age provides significant reductions in dead or dying intervertebral disc cells (F’’). The graph illustrates the results from the images, showing that Dasatinib and Quercetin treatment significantly reduces dead or dying, TUNEL-stained intervertebral disc cells in aged mice (F’’’). 

This Senolytic Drug Combination Diminishes the Presence of Blood Inflammatory Factors

Since inflammation accompanies age-related intervertebral disc degeneration, the scientists analyzed the presence of blood inflammatory molecules in aged mice after Dasatinib and Quercetin treatments. They found that even though inflammation increases in an age-dependent manner, Dasatinib and Quercetin treatment suppressed blood inflammatory factors. Notably, mice treated with the drugs between 6 and 23 months of age exhibited diminished blood inflammatory factors, and those treated from 14 to 23 months showed a decrease in a slightly different set of blood inflammatory molecules. These results suggest the two senolytic drugs mitigate disc degeneration, at least partially, by reducing inflammation.

Senolytic Treatment Improves Physical Performance During Aging

To measure how these tissue preservation and anti-inflammatory effects impacted physical performance, the team of scientists looked at a test of grip strength. They examined how much mice could pull a triangular metal bar that digitally registered the mouse grasp force — a readout of grip strength. Their results indicated that Dasatinib and Quercetin administration in mice ages 6 to 23 months significantly enhanced grasp force, meaning that the tissue-related benefits of the drugs translated to physical performance in mice.

(Risbud et al., 2021 | Research Square) Dasatinib and Quercetin treatment significantly improved grip strength. Mice given Dasatinib and Quercetin (D+Q) injections between ages 6 and 23 months exhibited significant improvements in their grasp force compared to untreated (Veh).

Intriguing Possibilities with Dasatinib and Quercetin Treatments

“Systemic administration of [Dasatinib and Quercetin] posits a new and exciting therapeutic approach to treating disc degeneration, without the inherent risks associated with invasive surgical interventions,” stated Risbud and colleagues. If these findings translate to humans, Dasatinib and Quercetin could be used to alleviate disc degeneration, reduce inflammation, and improve physical performance during aging in the future. It also means there could be a therapeutic time frame for the administration of the two senolytic drugs to obtain optimal benefits. Researchers will need to address the therapeutic time frame issue when planning future studies of lower back pain and intervertebral disc degeneration.