AUF1 Hat Trick: Suppresses Inflammation, Reduces Cancer Risk, and Inhibits Cellular Senescence
Researchers at NYU School of Medicine have, for the first time, identified a single gene that simultaneously controls inflammation, accelerated aging and cancer. _NYU SOMAUF1 is a micro-RNA binding protein that has been found to perform multiple vital cell functions. Engineered mice that lack the AUF1 protein suffer rapid premature aging that worsens with each generation. By replacing AUF1 function in these mice, the harmful premature aging and accelerated cellular senescense can be reversed.
AUF1 binds and strongly activates the transcription promoter for telomerase catalytic subunit Tert. In addition to directing inflammatory cytokine mRNA decay, AUF1 destabilizes cell-cycle checkpoint mRNAs, preventing cellular senescence. Thus, a single gene, AUF1, links maintenance of telomere length and normal aging to attenuation of inflammatory cytokine expression and inhibition of cellular senescence. _Molecular Cell (ScienceDirect)
AUF1 also accelerates the degradation of inflammatory cytokine, reducing the inflammation load on cells and tissues. More from NYU School of Medicine, where much of the recent research on AUF1 was done:
For decades, the scientific community has known that inflammation, accelerated aging and cancer are somehow intertwined, but the connection between them has remained largely a mystery, Dr. Schneider said. What was known, due in part to past studies by Schneider and his team, was that a gene called AUF1 controls inflammation by turning off the inflammatory response to stop the onset of septic shock. But this finding, while significant, did not explain a connection to accelerated aging and cancer.
When the researchers deleted the AUF1 gene, accelerated aging occurred, so they continued to focus their research efforts on the gene. Now, more than a decade in the making, the mystery surrounding the connection between inflammation, advanced aging and cancer is finally being unraveled.
The current study reveals that AUF1, a family of four related genes, not only controls the inflammatory response, but also maintains the integrity of chromosomes by activating the enzyme telomerase to repair the ends of chromosomes, thereby simultaneously reducing inflammation, preventing rapid aging and the development of cancer, Dr. Schneider explained.
“AUF1 is a medical and scientific trinity,” Dr. Schneider said. “Nature has designed a way to simultaneously turn off harmful inflammation and repair our chromosomes, thereby suppressing aging at the cellular level and in the whole animal.”
With this new information, Dr. Schneider and colleagues are examining human populations for specific types of genetic alterations in the AUF1 gene that are associated with the co-development of certain immune diseases, increased rates of aging and higher cancer incidence in individuals to determine exactly how the alterations manifest and present themselves clinically. _NYU
This is an exciting and potentially important finding. But it takes time for exciting research discoveries to be converted into potentially revolutionary therapies against cancer, aging, and crippling inflammatory diseases.
Early attempts to capitalise on this discovery are likely to be disappointing, particularly as expectations will tend to be raised prematurely. But as the ability to generate safe, effective, affordable treatments begins to catch up to the ability to discover the mechanisms of biological function at multiple levels, the pace of change may grow at a startling rate.
The important thing is to get the basic science findings into the hands of the research community for replication, clarification, and elaboration. After that, scientists can begin finding ways to make the research work in favour of an abundant human future.
Original 1997 identification of AUF1 at Rutgers and Wake Forest (PDF)