Cancer-Linked Gene Fuels Age-Related Inflammation, Raising Potential to Promote Healthy Aging

A gene known to cause cancer may also fuel chronic inflammation associated with aging, and a study found that suppressing it with an existing cancer drug improved measures of aging.

According to AZoLifeSciences on the 31st (local time), an international research team led by Sanford Burnham Prebys Medical Discovery Institute published the findings on the 20th in the journal Nature Aging.

The researchers focused on CCND1, the gene that produces cyclin D1, a protein that regulates cell proliferation. The gene drew attention in oncology after it was found in the early to mid-1990s that its overexpression could cause cancer.

The study began with the observation that the protein is also highly expressed in nonproliferating “senescent cells.” To prevent cancer, senescent cells stop dividing and secrete inflammatory substances that prompt immune cells to clear them. But as immune function declines with age, the cells accumulate and cause chronic inflammation.

The researchers analyzed 14 publicly available datasets and found that CCND1 was activated more often than other senescent-cell markers. Follow-up experiments also showed that cyclin D1, together with its partner molecule cyclin-dependent kinase 6 (CDK6), promotes DNA damage and strengthens the cells’ inflammatory tendency.

Lead author Adarsh Rajesh, a postdoctoral researcher at Cold Spring Harbor Laboratory, said, “Cyclin D1 and CDK6 promoted DNA damage, strengthening the inflammatory tendency of these cells.”

The researchers also observed cyclin D1 accumulation and increased expression of genes related to the secretion of inflammatory substances in the livers of older mice. Mice genetically engineered to prevent production of cyclin D1 had less DNA damage and lower expression of inflammatory genes as they aged.

Similar protective effects were seen in normal mice treated with palbociclib, which is approved by the U.S. Food and Drug Administration (FDA) as a targeted breast cancer therapy. The drug works by blocking the interaction between cyclin D1 and CDK6.

Rajesh said, “In addition to suppressing inflammation, it reduced frailty and improved function in older mice.” The researchers assessed motor coordination by testing the mice’s balance on a rotating rod and scored frailty based on a composite of more than 30 measures, including gait impairment, hearing loss and vision decline.

Peter Adams, a professor at Sanford Burnham Prebys, said, “The older mice treated with the drug were in much better condition than those that were not,” adding that the findings “suggest it has the ability to improve the health and function of older mice.”

Adams said, “It is very exciting to think that this drug could potentially be repurposed to promote healthy aging in humans,” adding that “repurposing this drug and similar drugs to treat age-related inflammatory diseases is a promising strategy that warrants further investigation.”