The 'Zombie Gene' That May Protect Elephants From Cancer

          This past Summer an article was released revealing the findings of Dr. Vincent J. Lynch and other scientists from the University of Chicago. These scientists have discovered a rare mutation in the genes of elephants while looking for a reason behind their small probabilities of cancer. This rare mutation starts in the p53 gene. The p53 gene, in short, is a tumor suppressant gene that inhibits the formation of tumors. p53 makes a protein that senses damaged DNA and responds by either repairing or by destroying the damaged cells.

          The evolved p53 gene in elephants reacts differently because when the protein senses damaged DNA, it does not even think about fixing it, the protein just automatically destroys them so they will not have a chance to reproduce their mutation. Not only do their p53 genes immediately eliminate the problem, but they also have so many more than humans. Humans only have one copy of p53 while elephants have 20 copies.
          The variation in the p53 gene sparked scientists to look a little deeper, which unearthed a very interesting mutation that explains why elephants are not as prone to cancer. Both humans and elephants have a gene called LIF. While humans have only one LIF gene, elephants seem to contain 10. After looking closer into these LIF genes scientists discovered one LIF6 gene, which is a gene that has been seen before in animals, but has been thought to have become extinct up until this discovery in modern day elephants. LIF6 has seemingly 'resurrected' itself, which is why scientists are referring to it as the 'Zombie Gene'.
          Normally when the proteins are released from the p53 gene, LIF genes are instructed to stop each damaged cell's production of proteins. However, LIF6 mutated in order to be able to read the protein made by p53, which makes LIF6 able to go in and actually kill the damaged cells instead of just impeding their ability of making proteins. LIF6 kills the cell by attacking the mitochondria, which turns out to be very poisonous to the cell. The mitochondria is ripped open, poisons the cell, and ultimately kills the cell.
          Although there are still many factors to look into, I think it is a wonderful beginning to a major study on the way the LIF6 gene works. To be able to see this gene live and in action could be very beneficial to discovering what we can do as far as medication in humans. I think this study could be the catalyst to many others in order to see what can be done to manipulate the gene in order to possibly take down one of the biggest forms of disease in our world today.

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Peptide targeting senescent cells restores health of aging mice

Scientists have found that regular infusions of a peptide can selectively seek out and destroy broken-down cells that inhibit proper tissue renewal. These cells are called senescent cells. They showed evidence of improving healthspan in naturally-aged mice and mice genetically engineered to rapidly age. This peptide took over four years of trial and error to develop. It works by blocking the ability of a protein implicated in senescence, FOXO4, to tell another protein, p53, not to cause the cell to self-destruct. By interfering with the FOXO4-p53 crosstalk, the peptide causes senescent cells to go through apoptosis, or cell suicide. The Results occurred at different times over the period of treatment. Fast-aging mice that had patches of missing fur began to regrow their fur after 10 days. After about three weeks, fitness and endurance benefits began to show, the older mice were running double the distance of their counterparts who did not receive the peptide. A month after treatment, aged mice showed an increase in markers indicating healthy kidney function. 
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Some Human Cancers Exhibit Low-grade Inflammation

Scientists from Hebrew University of Jerusalem were perplexed when they found that a specific research mouse model who had a mutation in the tumor suppressor gene p53, was oddly more cancer-prone post mutation. There was low-grade inflammation in the mouse's epithelial tissue (skin/blanket of cells covering the body with different shapes). Due to this inflammation, scientists treated it with non steroidal anti-inflammatories (NSAID), which as a result reduced its risk of cancer. For more in depth answers, Israeli researchers turned to University of California San Francisco's Dvir Aran, one of the contributors to the scientific paper,"Widespread parainflammation in human cancer". Aran and his colleagues worked alongside the researchers in Israel to piece the puzzle together.

With gene expression data collected, scientists found that four cancers had mutations of the p53 gene with higher parainflammation (PI) scores. These specific cancer types had poor prognoses meaning that PI could possibly speed up cancers.The new team found that there was an increased cellular response of 40 genes. This then led them to analyze data from about 800 human cancer cell lines, 6,500 tumor samples, and 18 different cancer types to see if any had this inflammatory response.

The NSAIDs were used to treat the mouse adenoidal organoids and two human cancer cell lines while expression of PI genes decreased by more than half, suggesting that this could help identify who could be treated with the NSAIDs, making scientists one step closer to finishing the puzzle.

http://www.the-scientist.com/?articles.view/articleNo/47100/title/Some-Human-Cancers-Exhibit-Low-grade-Inflammation/

Why is Elephant Cancer Rare? Answer Might Help Treat Humans

On Thursday, October 8, 2015 in the Journal of the American Medical Association, new studies were published about a cancer suppressing gene found in elephants and many other species.  Dr. Schiffman, a pediatric cancer specialist at the University of Utah, lead a team of researchers in a dealing with p53, a gene that prevents cancer in elephants as well as humans and other species.  Elephants possess a vast amount of p53 compared to humans and other species smaller than them.  This is because of a condition possessed by elephants called Li-Fraumeni syndrome (a syndrome that increases an elephant’s chance of developing cancer).  This syndrome is also found in other species including humans.  The p53 gene in species possessing it, cause unhealthy cells to self-destruct when affected with radiation or other carcinogens.  Dr. Schiffman’s team made comparisons of the effects of radiation to the cells of elephants, cells form ten healthy humans and ten human patients with Li-Fraumeni syndrome.  It was found that cells of the elephants self-destruct at a rate two times faster than that of healthy humans and humans with Li-Fraumeni syndrome.  This is because of the vast amount of copies of the gene that elephants possess.  Humans have only one gene compared to the elephants’ twenty copies.  Although cancer is rare in elephants, it does not mean that it does not exist.  Schiffman’s team found that although elephants sometimes live as long as humans do, only 1 in 20 dies of cancer as opposed to 1 in 4 humans dying from cancer.  

These findings can aid in gene therapy as well as help with the development of new drugs to treat those with cancer.  This could also be a breakthrough to help many with the many different cancers that are inherited from generation to generation. 

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