Senescent Cells as a Contributing Cause of Degenerative Disc Disease

At this point, I suspect it will surprise no-one who follows the field to learn that the accumulation of senescent cells is a significant cause of degenerative disc disease. The evidence from a mouse study that is provided in the open access paper here doesn't quite rise to establishing that claim, but it is compelling nonetheless. Given the role of cellular senescence in arthritis, a disease of localized chronic inflammation, it is logical to also expect a role in the degeneration of intervertebral discs, as this is also a condition of aging in which inflammation seems important.

Senescent cells, even while present in only comparatively small numbers, generate a potent mix of molecules that spurs chronic inflammation and is destructive of surrounding tissue structure. Fortunately early senolytic compounds, those shown to destroy a sizable fraction of senescent cells cells in animal studies, are cheap and readily available to anyone willing to try this self-experiment. It is just a pity that so few older people know this at the present time - the hundreds of millions worldwide who are suffering when perhaps they need not be.

Age-related changes in the intervertebral discs are the predominant contributors to back pain, a common physical and functional impairment experienced by older persons. Cellular senescence, a process wherein cells undergo growth arrest and chronically secrete numerous inflammatory molecules and proteases, has been reported to cause decline in the health and function of multiple tissues with age. Although senescent cells have been reported to increase in intervertebral degeneration (IDD), it is not known whether they are causative in age-related IDD.

To examine the impact of senescent cells on age-associated IDD, we used p16-3MR transgenic mice, which enables the selective removal of p16Ink4a-positive senescent cells by the drug ganciclovir. Disc cellularity, aggrecan content and fragmentation alongside expression of inflammatory cytokine (IL-6) and matrix proteases (ADAMTS4 and MMP13) in discs of p16-3MR mice treated with ganciclovir and untreated controls were assessed. In aged mice, reducing the percent of senescent cells decreased disc aggrecan proteolytic degradation and increased overall proteoglycan matrix content along with improved histological disc features. Additionally, reduction of senescent cells lowered the levels of MMP13, which is purported to promote disc degenerative changes during aging.

The findings of this study suggest that systemic reduction in the number of senescent cells ameliorates multiple age-associated changes within the disc tissue. Cellular senescence could therefore serve as a therapeutic target to restore the health of disc tissue that deteriorates with age.