The hidden role of a cell-cycle regulator in senescent cells that don't divide
In a tale of identities as divergent as "The Prince and the Pauper," a well-known cancer-causing gene also influences cells in a zombie-like state meant to prevent cancer.
The gene CCND1, which produces the protein cyclin D1, plays a crucial role in senescent cells—those that no longer divide and instead aim to prevent cancer. Despite its typical association with cancer due to its role in cell cycle regulation, cyclin D1 is also highly expressed in these non-proliferating cells. This raises the question: why is a cancer-promoting gene active in cells that should not proliferate?
Senescent cells tackle cancer by halting cell cycle progression and releasing inflammatory molecules to alert the immune system. However, aging impairs the immune system's ability to clear these cells, leading to chronic inflammation associated with age-related diseases. The research team investigated whether cyclin D1 had a unique function in promoting chronic inflammation in senescent cells, distinct from its role in cell cycle control.
Their findings confirmed that cyclin D1, acting together with its partner molecule cyclin-dependent kinase 6 (CDK6), contributed to sustained inflammatory signaling in senescent cells. Additionally, they discovered that elevated levels of cyclin D1 accumulated in the livers of aging mice, mirroring the cellular effects observed in their laboratory experiments.
To test the necessity of cyclin D1, the scientists compared normal mice to genetically modified mice unable to produce cyclin D1. Aged livers from the latter group exhibited reduced DNA damage and lower expression of inflammatory genes. Furthermore, when treated with palbociclib—a drug that inhibits cyclin D1-CDK6 interaction—they observed that normal mice experienced less DNA damage, reduced inflammatory gene expression, and improved overall function, including better motor coordination.
Palbociclib is already approved by the FDA for treating certain breast cancers. The researchers suggest that repurposing this drug or similar compounds could offer a promising strategy to enhance the health and functional capacity of older individuals by mitigating age-related inflammation and its associated health decline.
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