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SAN DIEGO, CA – Researchers have made a significant stride in understanding and potentially mitigating chronic inflammation, a hallmark of aging, by focusing on “zombie-like” cells that accumulate over time. A recent study published in Nature Communications reveals how a crucial DNA repair protein, p53, can suppress the inflammatory activity of these senescent cells, potentially paving the way for therapies that promote healthier aging.
As we age, cells can enter a state of senescence, where they no longer divide but remain in the body. These senescent cells, often referred to as “zombie cells,” release inflammatory molecules through a process known as the senescence-associated secretory phenotype (SASP). This chronic, low-grade inflammation, or “inflammaging,” is linked to numerous age-related diseases.
Scientists at Sanford Burnham Prebys and their collaborators discovered that the mitochondria, the powerhouses of cells, play a critical role in regulating p53’s ability to suppress SASP. By inducing senescence in human cells through radiation, the researchers demonstrated that p53 effectively inhibited SASP and the formation of cytoplasmic chromatin fragments (CCF), which are damaged DNA fragments that trigger immune responses.
“In addition to no longer growing and proliferating, the other hallmark of senescent cells is that they have this inflammatory program causing them to secrete inflammatory molecules,” said Peter Adams, Ph.D., director and professor of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and senior and co-corresponding author of the study.
The team further validated their findings in mice by using a drug that activates p53. While the drug didn’t reduce the number of senescent cells, it did reverse the cellular signature of age-associated SASP, suggesting a potential method for curbing inflammatory pollution.
The study also highlighted the role of mitochondrial dysfunction in senescent cells. Stressed mitochondria can lead to the formation of CCF and suppress the expression of p53.
“Altogether, we’ve identified a cellular circuit capable of promoting DNA repair and genome integrity while suppressing the dangerous inflammatory feature of senescent cells that contribute to age-related diseases,” said Karl Miller, Ph.D., staff scientist in the Adams lab at Sanford Burnham Prebys and lead and co-corresponding author of the study. “We also have shown that this pathway can be modified by existing drugs in cultured cells and mice, so it may be possible to one day design a treatment that targets p53 to promote healthier aging.”
The research suggests that targeting p53 could offer a promising avenue for developing therapies to combat age-related inflammation and promote longevity. However, further studies are needed to translate these findings into effective treatments for humans.
Disclaimer: This news article is based on research findings and should not be interpreted as medical advice. The information provided is for educational purposes only. Always consult with a qualified healthcare professional before making any decisions about your health or treatment. The research described is still in its early stages, and results obtained in cellular and animal models may not necessarily translate to humans.
