A Medical and Scientific Trinity: AUF1 gene


Scientists have known for decades that accelerated ageing, inflammation and cancer are somehow related, yet exactly how these conditions are linked has so far been unknown.

One recent study, conducted by Robert J. Schneider, PhD, the Albert Sabin Professor of Molecular Pathogenesis and associate director for translational research and co-director of the Breast Cancer Program at the NYU Langone Medical Center,  published ahead of the 13 July print edition in Molecular Cell reveals that AUF1 gene that controls chronic inflammations simultanneusly controls accelerated aging and cancer. Dr. Schneider, the principal investigator of the study, said it’s an exciting scientific find.This was certainly an unexpected finding, because the two, if not regulated properly, can eventually lead to cancer development.

Schneider’s previous studies shown that a gene called AUF1 controls inflammation by switching off the inflammatory response to prevent the onset of septic shock. Although this finding is significant, it failed to shed light on the link to ageing and cancer. The team observed that accelerated ageing occurred when the AUF1 gene was deleted, which led them to investigate further. A decade later, they have finally discovered the link between inflammation, advanced aging and cancer.

It was found that AUF1 gene, which belongs to a family of four related genes, also maintained the integrity of chromosomes by activating telomerase, an enzyme, to repair the ends of chromosomes. and in this way AUF1 simultaneously reduces inflammation, prevents rapid aging and cancer from developing.

English: An illustration of a telomerase molecule

English: An illustration of a telomerase molecule (Photo credit: Wikipedia)

Studies conducted on mice suggested that AUF1-deficient mice undergo striking telomere erosion, markedly increased DNA damage responses at telomere ends, pronounced cellular senescence, and rapid premature aging that increases with successive generations.  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.

Dr. Schneider explained: “AUF1 is a medical and scientific trinity. 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.”

Dr. Schneider and his team are currently researching how the alterations manifest and present themselves clinically. They are examining human populations for specific types of genetic changes in the AUF1 gene, which are associated with rapid ageing, higher risk of cancer and co-developments of certain immune diseases.

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