Targeting Cellular Senescence Could Halt Age-Related Bone Loss

Inhibiting cellular senescence could be a novel therapeutic strategy to prevent bone loss and other age-related diseases, according to a mini-review recently published in The Journal of Clinical Endocrinology & Metabolism.

Researchers led by Sundeep Khosla, MD, of the Mayo Clinic in Rochester, Minn., write that while life expectancy now is longer than ever, age-related osteoporosis is a growing health problem. In 2000, there were about 9 million osteoporotic fractures and by 2050 the incidence of hip fracture is expected to increase by 240 percent in women and by 310 percent in men, according to the authors. “To put this in further context, the number of women who will experience a fracture in 1 year exceeds the combined number of women who will experience incident breast cancer, myocardial infarction, or stroke,” they write.

Age-related osteoporosis often exists with other comorbidities like atherosclerosis and diabetes. Aging itself is the leading risk factor for these diseases, so the authors point to the “Geroscience Hypothesis,” which posits that manipulating fundamental aging mechanisms can delay the appearance or severity of these age-related diseases. One of these fundamental aging mechanisms is cellular senescence, so the researchers wanted to focus on senescence’s role in mediating age-related bone loss. The authors also write that there is declining interest by the pharmaceutical industry in developing new osteoporosis drugs. “However,” they write, “placing osteoporosis in the context of treating multiple aging conditions offers perhaps renewed hope for new drug development for this important age-associated disease.”

Using their own knowledge of the field and PubMed searches, the researchers found compelling evidence that there is an increase in senescent cells in the bone microenvironment with aging. “These cells produce a proinflammatory secretome that leads to increased bone resorption and decreased bone formation, and approaches that either eliminate senescent cells or impair the production of their proinflammatory secretome have been shown to prevent age-related bone loss in mice,” the authors write.

The authors conclude this review by writing: “Targeting cellular senescence represents a new therapeutic paradigm for preventing or even reversing age-related osteoporosis and simultaneously treating multiple aging comorbidities. This approach does not focus specifically on bone but rather on a fundamental aging mechanism operative across tissues. If the remarkable promise of preclinical models is realized in human studies, we may truly have a novel approach to enhance healthspan (and perhaps lifespan) in the rapidly growing aging population in the Unites States and throughout the world.”

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