Role of protein D1 in aging cells has been revealed

The CCND1 gene encodes the protein cyclin D1, which normally controls the cell’s transition to division; it activates signaling molecules necessary for DNA replication and subsequent division. In cancer cells, this system gets out of control, and cyclin D1 becomes the cause of uncontrolled growth. In senescent (aging) cells, there is no division: they are deliberately frozen in a stable phase of the cell cycle to prevent them from becoming cancerous.

At the same time, they activate another defense mechanism: they begin to secrete inflammatory molecules (this is called the senescence‑associated secretory phenotype, or SASP) to attract the immune system’s attention and be removed. As we age, immune surveillance weakens, senescent cells accumulate, and chronic inflammation grows along with them.

Researchers noticed an oddity: cyclin D1 remains highly active in senescent cells, even though there is no division occurring there. To determine whether it has a distinct function in these cells, the team analyzed data from 14 public datasets covering various models and types of senescence. It turned out that CCND1 is even more common than classical senescence markers. Further experiments confirmed that cyclin D1 is not just present but actively supports the tendency of senescent cells to release inflammatory molecules.

As the author of the study, Adarsh Rajesh, explained, cyclin D1, together with cyclin‑dependent kinase 6 (CDK6), enhances the inflammatory tendencies of senescent cells, provoking DNA damage.

The accumulation of cyclin D1 was observed in the aging liver of mice. In cells with an excess of it, the expression of genes associated with the release of inflammatory molecules (SASP) increased. To determine how essential cyclin D1 is for this process, the researchers compared normal mice with genetically modified ones in which cyclin D1 was not produced. In older mice without cyclin D1, there was less DNA damage and a lower level of inflammatory gene expression — in other words, the inflammation was weaker.

Then they tested the effect of the drug palbociclib, which blocks the interaction between cyclin D1 and CDK6. In ordinary old mice, this drug had a similar protective effect: it reduced inflammation and at the same time reduced the manifestations of frailty and improved functional performance.

The effectiveness was assessed by several parameters. Motor coordination was tested using a rotating rod, and the mice had to keep their balance. Senility was assessed by a complex score that took into account more than 30 indicators, from the severity of gait disorders to hearing loss and visual impairment. During treatment, the old mice performed noticeably better on tests than their peers without therapy.

Palbociclib has already been approved by the FDA for the treatment of certain forms of breast cancer. Now, scientists see potential in it: it could be used to reduce age‑related inflammation and improve quality of life in old age. As the study leader, Peter Adams, emphasizes, the idea of using such drugs to combat age‑related inflammatory conditions looks promising, but it requires further research.