Project 443713

Painful degeneration of the spine is one of the most common disabilities in young and middleaged professionals. However, very little is known about the cause of this pain and no early treatment options are currently available. In the body, all normal cells have a limited number of cell divisions where after they permanently stop dividing, they become "senescent". Senescent cells therefore build up in our tissues as we age. The number of senescent cells can drastically increase prematurely following DNA damaged, injury, cytokine exposure or cellular stress. This is called "premature stress induced senescence". Senescent cells were long thought to be inactive bystanders, however more recent discoveries have shown that they actively contribute to illnesses such as cancer, arthritis, and diabetes. Ageing and degenerating discs in the spine accumulate senescent cells where they act as small factories spewing out factors causing pain and inflammation along with enzymes that degrade the tissue. They also create an environment that prevents the heathy cells from building new tissue, and they may directly contribute to back pain. Recent studies in mice have shown that clearing of senescent cells slows many age-related problems which has a marked positive effect on spine health in older animals. There are several emerging drugs that remove senescent cells or that interfere with the effects of senescent cells coming close to clinical studies. Here we will test two drugs in intact human IVDs from organ donors as well as in a validated mouse model of back pain.