Senescent cell accumulation appears to be a major player in the pathology of most of the joint-related issues that occur in older individuals. Senescent cells secrete signals that provoke a state of chronic inflammation, alter nearby cell behavior, and disrupt tissue structure and maintenance. Clearance of these cells reverses numerous age-related conditions and measures of aging in mice. Hence the advent of senolytic therapies that selectively destroy senescent cells is a much anticipated development in medicine. Indeed, the first such therapies are pre-existing drugs, such as the dasatinib and quercetin combination, are already in human trials, producing promising initial data, and in principle available to any individual who can convince a physician to write an off-label prescription.
Aging is one of the major risk factors for degenerative joint disorders, including those involving the temporomandibular joint (TMJ). TMJ degeneration occurs primarily in the population over 65, significantly increasing the risk of joint discomfort, restricted joint mobility, and reduced quality of life. Unfortunately, there is currently no effective mechanism-based treatment available in the clinic to alleviate TMJ degeneration with aging.
We now demonstrate that intermittent administration of the senolytic combination of dasatinib and quercetin, which can selectively clear senescent cells, preserved mandibular condylar cartilage thickness, improved subchondral bone volume and turnover, and reduced Osteoarthritis Research Society International (OARSI) histopathological score in both 23- to 24-month-old male and female mice. Senolytics had little effect on 4 months old young mice, indicating age-specific benefits.
Our study provides proof-of-concept evidence that age-related TMJ degeneration can be alleviated by pharmaceutical intervention targeting cellular senescence. Since the senolytics used in this study have been proven relatively safe in recent human studies, our findings may help justify future clinical trials addressing TMJ degeneration in old age.