Category Archives: Gene Medicine

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Professor David Porteous predicts that gene medicines such as gene therapy will improve the effectiveness of treating psychiatric disorders.

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I use the phrase 'gene medicine' to refer to medicines that are developed through gene knowledge. They come in lots of different forms. A classic form, if you like, is gene therapy where you actually use the gene itself as a form of therapeutic to manufacture a damaged protein that an individual may be lacking. But more broadly, and I think more relevant to the area of schizophrenia, is the idea of using gene knowledge to make more rational forms of treatment. Now just take the example of having identified a gene a risk factor in schizophrenia and that risk factor turns out to have something to do with the way in which we receive signals in the brain and that process is disordered. If we can understand that basis of that, we can start making much more finely tuned pharmaceuticals than we currently use and ones with far fewer side effects, which is one of the biggest problems in this area. So reducing side effects and improving the effectiveness of treatments is something which I believe will come out of gene knowledge.

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gene, medicine, therapy, pharmaceutical, risk, factor, psychiatric, cognitive, disorder, side, effects, protein, brain, david, porteous

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Gene Medicine :: DNA Learning Center

Individuals with this altered gene have hereditary hypertension (high blood pressure) and at the same time a skeletal malformation called brachydactyly type E, which is characterized by unusually short fingers and toes. The effect on blood pressure is so serious that -- if left untreated -- it most often leads to death before age fifty. After more than 20 years of research, scientists of the Experimental and Clinical Research Center (ECRC), a joint cooperation between the MDC Max Delbrck Center for Molecular Medicine in the Helmholtz Association and the Charit -- Universittsmedizin Berlin have now identified the gene that causes this rare syndrome. In six families not related to each other they discovered different point mutations in the gene encoding phosphodiesterase-3A (PDE3A). These mutations always lead to high blood pressure and shortened bones of the extremities, particularly the metacarpal and metatarsal bones. This syndrome is the first Mendelian hypertension form (salt-resistant) not based on salt reabsorption but instead is more directly related to resistance in small blood vessels.

"In 1994, when we began with the study of this disease and examined the largest of the affected families in Turkey for the first time, modern DNA sequencing methods did not yet exist. Extensive gene databases to facilitate the search for the cause of this genetic disease were also lacking back then," said PD Dr. Sylvia Bhring, senior author of the research group's publication headed by Professor Friedrich C. Luft.

"Veritable treasure trove for genetics"

In 1996, the research group succeeded in comparing the genetic material of healthy and diseased family members in order to localize the chromosome region where this disease gene must reside. The region they detected was on a segment of chromosome 12 and was an estimated 10 million base pairs in size. "Ultimately however," said Dr. Bhring, "a 16-year-old Turkish boy helped us to pinpoint this gene. He is a veritable treasure trove for the field of genetics." He also has severe high blood pressure -- like all other test subjects he is being treated anti-hypertensive drugs -- but his hands are nearly normal. Only the metacarpal bones of his little fingers are slightly shortened.

Whole-genome sequencing of the DNA from several people with the syndrome recently enabled Dr. Philipp G. Maass, Dr. Atakan Aydin, Professor Luft, Dr. Okan Toka (formerly MDC/Charit, now the University of Erlangen), Dr. Carolin Schchterle (MDC research group Dr. Enno Klumann) and Dr. Bhring to identify the gene and six different point mutations in a total of six families from around the world. It is the gene PDE3A, which contains the blueprint for the enzyme, phosphodiesterase 3A. The six different point mutations, which the researchers pinpointed in the PDE3A gene, lead to the exchange of a single DNA building block that is different in each family. In each case, one amino acid of the enzyme is exchanged.

One gene -- two different syndromes

But how can one mutated gene cause two quite different diseases such as hypertension and brachydactyly? The ECRC researchers also provide the explanation for this in their study. The task of the phosphodiesterase encoded by the PDE3A gene is to control the quantity of the two secondary messenger proteins present in each cell, cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate), and thus to regulate the duration of their activity.

The mutations in the gene PDE3A, however, cause the enzyme phosphodiesterase to be overexpressed. Thus, it modulates too much of the secondary messenger protein cAMP (cyclic adenosine monophosphate) into AMP (adenosine monophosphate). As a result, the cell has less cAMP at its disposal. The consequence is that, in the affected family members, the smooth muscle cells of the vascular wall of small arteries divide to a greater extent. This proliferation leads to a thickening of the vascular muscle layer, and the blood vessels narrow and stiffen, resulting in high blood pressure. Furthermore, a too low cAMP level in the vascular muscle cells also leads to increased narrowing of the blood vessels.

But what effect do the lowered cAMP levels have on the development of the bones of the extremities? The gene that elicits the skeletal malformation brachydactyly type E is PTHLH (parathyroid hormone-like hormone). In the cartilage cells, a transcription factor (CREB), activated by cAMP, binds in the control region of the gene. This factor ensures that the gene is transcribed and can affect the growth of the cartilage. If there is less cAMP in the cartilage cell, this mechanism is disturbed. This situation then leads to the shortening of the metacarpals and metatarsals, namely the fingers and toes. Thus, by varying the cellular signal transduction, one point mutation can elicit two different characteristics in one and the same person.

New perspectives on hypertension development

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Gene responsible for hypertension, brachydactyly ...

HOUSTON - (April 13, 2015) - For decades, scientists and physicians have puzzled over the fact that infants with the postnatal neurodevelopmental disorder Rett syndrome show symptoms of the disorder from one to two years after birth.

In a report in the Proceedings of the National Academy of Sciences, Dr. Huda Zoghbi and her colleagues from Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, unravel the mystery by looking at when and how the causal gene involved (methyl-CpG binding protein 2 or MECP2) binds to methylated cytosine over the course of brain development.

Using mice in which the MeCP2 protein is tagged with a fluorescent green protein, they determined genome-wide MeCP2 binding profiles in the adult animal brain. In addition to the expected finding of MeCP2 binding to methylated cytosine with guanine (CG) with high affinity, they also found that MeCP2 binds to cytosine when it is followed by either adenine, cytosine or thymine instead of guanine (non-CG methylation or "mCH").

"This pattern is unique to the maturing and adult nervous system," said Zoghbi. She noted that genes that accumulate non-CG methylation after birth are preferentially dysregulated in mouse of models of diseases associated with the lack of, or elevations, of the MeCP2 protein.

"This suggests that MeCP2 binds to newly established methylated cytosine followed by any base other than a guanine as neurons mature to enact its function of regulating gene expression," said Zoghbi

The study provides insight into the molecular mechanism that governs MeCP2 and also gives a rationale for why the symptoms occur at least a year after birth.

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Others who took part in this work include Drs. Lin Chen, Kaifu Chen, Laura A. Lavery, Steven Andrew Baker, Chad Shaw and Wei Li, all of Baylor College of Medicine. Zoghbi is director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and a Howard Hughes Medical Institute investigator.

Funding for this work came from the Genomic and RNA Profiling Core at Baylor College of Medicine and National Institutes of Health Grant P30HD024064 (Intellectual and Developmental Disabilities Research Center) to generate the datasets; National Institutes of Health Grant 5R01NS057819 (to H.Y.Z.); National Institutes of Health Grant HG007538 (to W.L.); Cancer Prevention Research Institute of Texas Grants RP110471 and RP150292 (to W.L.) and the Howard Hughes Medical Institute.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Mystery of Rett timing explained in MeCP2 binding

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Newswise PHILADELPHIA The laboratory of David Weiner, PhD, a professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania, received the 2015 Vaccine Industry Excellence Award for Best Academic Research Team, at the World Vaccine Congress in Washington, DC this week. The Congress is an annual meeting of vaccine professionals from industry, academia, and non-profit organizations.

It is a great honor to receive this important award, especially with such an exceptional field of deserving finalists, says Weiner. This award is testimony to the many wonderful scientists who I have been lucky to have had pass through my laboratory, as well as those that I have been fortunate to collaborate with from academia or industry, and to the exceptional research environment present at Penn.

The Weiner lab's DNA vaccines program was chosen over other finalists from Duke University, Harvard Medical School, and the Memorial Sloan-Kettering Cancer Center by hundreds of vaccine stakeholders who voted for those most deserving of recognition for their work across 14 vaccine-related categories.

This award, given annually to the research group that has produced products with a novel mode of action, seen them progress into human trials, and can demonstrate significant supportive research grants, was given to Weiner and his lab for making significant contributions to the field of DNA vaccines.

Weiner is also chair of the Gene Therapy and Vaccine Program and co-leader of Tumor Virology Program in the Abramson Cancer Center.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.9 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $409 million awarded in the 2014 fiscal year.

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Research Team from Penn Receives Vaccine Industry Excellence Award

Study advances understanding of neurological circuits that might be targeted to treat anorexia nervosa

Building on their discovery of a gene linked to eating disorders in humans, a team of researchers at the University of Iowa has now shown that loss of the gene in mice leads to several behavioral abnormalities that resemble behaviors seen in people with anorexia nervosa.

The team, led by Michael Lutter, MD, PhD, assistant professor of psychiatry in the UI Carver College of Medicine, found that mice that lack the estrogen-related receptor alpha (ESRRA) gene are less motivated to seek out high-fat food when they are hungry and have abnormal social interactions. The effect was stronger in female mice, which also showed increased obsessive-compulsive-like behaviors.

The study also shows that ESRRA levels are controlled by energy status in the mice. Restricting calorie intake to 60 percent of normal over several days significantly increased levels of ESRRA in the brains of normal mice.

"Decreased calorie intake usually motivates animals, including humans, to seek out high-calorie food. These findings suggest that loss of ESRRA activity may disrupt that response," Lutter says.

Anorexia nervosa and bulimia nervosa are common and severe mental illnesses. Lutter notes that although 50 to 70 percent of the risk of getting an eating disorder is inherited, identifying the genes that mediate this risk has proven difficult.

ESRRA is a transcription factor - a gene that turns on other genes. Lutter and his colleagues previously found that a mutation that reduces ESRRA activity is associated with an increased risk for eating disorders in human patients. Although ESRRA is expressed in many brain regions that are disrupted in anorexia, almost nothing was known about its function in the brain. In the new study, published online April 9 in the journal Cell Reports, Lutter's team manipulated ESRRA in mice to investigate the gene's role in behavior.

"This work identifies estrogen-related receptor alpha as one of the genes that is likely to contribute to the risk of getting anorexia nervosa or bulimia nervosa," Lutter says. "Clearly social factors, particularly the western ideal of thinness, contribute the remaining 'non-genetic' risk, and the increasing rate of eating disorders over the past several decades is likely due to social factors, not genetics," he adds.

Through a series of experiments with genetically engineered mice, Lutter and his team showed that mice without the ESRRA gene have behavioral abnormalities related to eating and social behavior. In particular, mice without ESRRA show reduced effort to work for high-fat food when they are hungry. The mice also exhibited impaired social interaction and female mice without the gene show increased compulsive grooming, which may mimic obsessive-compulsive-type behavior in humans.

In order to refine their understanding of the effects of ESRRA in the brain, the researchers selectively removed the gene from particular brain regions that have been associated with eating disorders. They found that removing the gene from the orbitofrontal cortex was associated with increased obsessive-compulsive-type behaviors in female mice, while loss of ESRRA from the prefrontal cortex produced mice that were less willing to work to get high-fat food when they were hungry.

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Gene loss creates eating disorder-related behaviors in mice

Using induced pluripotent stem cells (iPSCs), a team led by Mount Sinai researchers has gained new insight into genetic changes that may turn a well known anti-cancer signaling gene into a driver of risk for bone cancers, where the survival rate has not improved in 40 years despite treatment advances.

The study results, published today in the journal Cell, revolve around iPSCs, which since their 2006 discovery have enabled researchers to coax mature (fully differentiated) bodily cells (e.g. skin cells) to become like embryonic stem cells. Such cells are pluripotent, able to become many cell types as they multiply and differentiate to form tissues. The iPSCs can then be converted again as needed into differentiated cells such as heart muscle, nerve cells, bone, etc.

While some seek to use iPSCs as replacements for cells compromised by disease, the new Mount Sinai study sought to determine if they could serve as an accurate model of genetic disease "in a dish." In this context, the dish stands for a self-renewing, unlimited supply of iPSCs or a cell line - which enables in-depth study of disease versions driven by each person's genetic differences. When matched with patient records, iPSCs and iPSC-derived target cells may be able to predict a patient's prognosis and whether or not a given drug will be effective for him or her.

In the current study, skin cells from patient with and without disease were turned into patient-specific iPSC lines, and then differentiated into bone-making cells where both rare and common bone cancers start. This new bone cancer model does a better job than previously used mouse or cellular models of "recapitulating" the features of bone cancer cells driven by key genetic changes.

"Our study is among the first to use induced pluripotent stem cells as the foundation of a model for cancer," said lead author Dung-Fang Lee, PhD, a postdoctoral fellow in the Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai. "This model, when combined with a rare genetic disease, revealed for the first time how a protein known to prevent tumor growth in most cases, p53, may instead drive bone cancer when genetic changes cause too much of it to be made in the wrong place."

Rare Disease Sheds Light on Common Disease

The Mount Sinai disease model research is based on the fact that human genes, the DNA chains that encode instructions for building the body's structures and signals, randomly change all the time. As part of evolution, some code changes, or mutations, make no difference, some confer advantages, and others cause disease. Beyond inherited mutations that contribute to cancer risk, the wrong mix of random, accumulated DNA changes in bodily (somatic) cells as we age also contributes to cancer risk.

The current study focused on the genetic pathways that cause a rare genetic disease called Li-Fraumeni Syndrome or LFS, which comes with high risk for many cancers in affected families. A common LFS cancer type is osteosarcoma (bone cancer), with many diagnosed before the age of 30. Beyond LFS, osteosarcoma is the most common type of bone cancer in all children, and after leukemia, the second leading cause of cancer death for them.

Importantly, about 70 percent of LFS families have a mutation in their version of the gene TP53, which is the blueprint for protein p53, well known by the nickname "the tumor suppressor." Common forms of osteosarcoma, driven by somatic versus inherited mutations, have also been closely linked by past studies to p53 when mutations interfere with its function.

Rare genetic diseases like LFS are good study models because they tend to proceed from a change in a single gene, as opposed to many, overlapping changes seen in more related common diseases, in this case more common, non-inherited bone cancers. The LFS-iPSC based modeling highlights the contribution of p53 alone to osteosarcoma.

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Stem cell disease model clarifies bone cancer trigger

A leading gene candidate that has been the target of breast cancer drug development may not be as promising as initially thought, according to research published in open access journal Genome Medicine.

Mutation in the gene PIK3CA is the second most prevalent gene mutation in breast cancer and is found in 20% of all breast cancers. This has led people to think these changes may be driving breast cancer. Yet these mutations are also known to be present in neoplastic lesions -pre-cancerous growths many of which are thought to be benign, that have not invaded the surrounding tissue.

Researchers from Stanford University wanted to better understand these neoplastic growths and how they related to the carcinoma. They sequenced the genes from tissue taken from the breasts of six women who had undergone a mastectomy, leading to a total of 66 samples, which included 18 carcinomas and 34 neoplastic lesions.

A specific mutation in the PIK3CA gene occurs in the same patient multiple times. This was found to be the case for four out of the six women. In two out of these four cases, this mutation occurs in the neoplastic lesions, which are not considered tumors, but does not occur in the invasive carcinoma.

One of the lead researchers, Arend Sidow, said: "There are currently several drugs in development that target PIK3CA, attesting to the fact that many companies and clinicians believe PIK3CA to be a promising target. Our finding that PIK3CA may recur multiple times at various stages of tumor or neoplastic development suggests that it is more of a moving target than one would like."

The researchers constructed phylogenetic trees to track the mutations back to their original cell to determine how the lesions were related to each other. From this, the researchers discovered that in each of the four PIK3CA-positive patients the mutation arose independently multiple times. This is something that has never been seen before. Following the PIK3CA mutation through these phylogenetic trees, and its lack of presence in the final carcinoma in two cases, would suggest that it is not driving the cancer, and instead suggests that it is a driver of benign proliferation.

This new information will have implications for the development of future drugs that target PIK3CA. Future studies should attempt to replicate this one with more patients and attempt to show whether PIK3CA mutations are ancestrally present in the tumor cells of positive patients, in which case it may be good target, or whether it is present in only a subset of tumor cells, in which case it is not a good target.

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We may be looking at wrong mutation for breast cancer treatment

Researchers at Upstate Medical University and Harvard University have linked the loss of key gene, WAVE1, to a lethal form of prostate cancer, according to a study published in the journal Oncotarget.

Prostate cancer is the most common form of cancer in men and is responsible for 27,000 deaths annually. About 220,000 new cases of prostate cancer are diagnosed each year.

Using bioinformatic meta-analysis to compare several publicly available databases, researchers found that alterations in the WAVE1 gene were associated with a shorter period of remission in patients who were treated for prostate cancer. Strikingly, the study also showed that 22.9 percent of the prostate cancers reviewed in the database harbored the WAVE1 gene deletion.

"We observed that prostate cancer tumors contain a frequent deletion of the WAVE 1 gene. What's important, though, is that this WAVE1 gene deletion occurs in metastatic and lethal cancer, thus suggesting that, the WAVE1 gene loss may represent an aggressive subtype of prostate cancer which is more challenging to treat and more likely to progress," said study coauthor Leszek Kotula, MD, Ph.D., associate professor of urology and biochemistry and molecular biology at Upstate Medical University in Syracuse, N.Y. "It is possible that patients who have tumors characterized by the deletion of the WAVE1 gene may benefit from earlier intervention, such as surgery or radiation therapy."

WAVE gene complexes are involved in cell motility and migration, cellular adhesion and cell-to-cell communication, numerous processes that can play a role in tumor progression and metastasis. "It is clear that disruption of the WAVE complex is associated with human cancers, including prostate cancer. However, what we have determined is that because lethal prostate cancers show this disruption, we may be able to identify mechanisms that lead to the tumor cell acquiring resistance to advanced therapies. Nonetheless, understanding the biological consequences of this deletion will require further investigation," said study coauthor Adam G. Sowalsky, Ph.D., instructor in medicine at Harvard Medical School.

The study, published in Oncotarget March 31, was funded by the National Institutes of Health and Department of Defense. Primary authors are Leszek Kotula, M.D., Ph.D., associate professor of urology and biochemistry and molecular biology; and Adam G. Sowalsky, Ph.D., instructor in medicine at Harvard Medical School. Other authors of the study include Dr. Pier Paolo Pandolfi, Dr. Steven Balk, Rachel Schaefer (Harvard Medical School, Boston, MA), and Dr. Gennady Bratslavsky and Rebecca Sager (Upstate Medical University, Syracuse, NY).

The study builds on earlier research (funded by the Department of Defense and the Kirby Foundation, Morristown, N.J.) by Kotula that implicated another gene, ABI1, as a tumor suppressor in prostate cancer. For the Oncotarget study researchers sought to find other genes that cooperate with ABI1 in the progression of prostate cancer, thus finding the WAVE1 gene as a culprit.

Kotula said his lab is now replicating the gene deletion in mice. Such work can aid in the development of drugs or new treatments to suppress tumors or provide more precision in the treatment of these aggressive cancers.

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The above story is based on materials provided by SUNY Upstate Medical University. Note: Materials may be edited for content and length.

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Subtype of lethal prostate cancer discovered by researchers

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Newswise SYRACUSE, N.Y. Researchers at Upstate Medical University and Harvard University have linked the loss of key gene, WAVE1, to a lethal form of prostate cancer, according to a study published in the journal Oncotarget.

Prostate cancer is the most common form of cancer in men and is responsible for 27,000 deaths annually. About 220,000 new cases of prostate cancer are diagnosed each year.

Using bioinformatic meta-analysis to compare several publicly available databases, researchers found that alterations in the WAVE1 gene were associated with a shorter period of remission in patients who were treated for prostate cancer. Strikingly, the study also showed that 22.9 percent of the prostate cancers reviewed in the database harbored the WAVE1 gene deletion.

We observed that prostate cancer tumors contain a frequent deletion of the WAVE 1 gene. What's important, though, is that this WAVE1 gene deletion occurs in metastatic and lethal cancer, thus suggesting that, the WAVE1 gene loss may represent an aggressive subtype of prostate cancer which is more challenging to treat and more likely to progress, said study coauthor Leszek Kotula, MD, Ph.D., associate professor of urology and biochemistry and molecular biology at Upstate Medical University in Syracuse, N.Y. It is possible that patients who have tumors characterized by the deletion of the WAVE1 gene may benefit from earlier intervention, such as surgery or radiation therapy."

WAVE gene complexes are involved in cell motility and migration, cellular adhesion and cell-to-cell communication, numerous processes that can play a role in tumor progression and metastasis. It is clear that disruption of the WAVE complex is associated with human cancers, including prostate cancer. However, what we have determined is that because lethal prostate cancers show this disruption, we may be able to identify mechanisms that lead to the tumor cell acquiring resistance to advanced therapies. Nonetheless, understanding the biological consequences of this deletion will require further investigation, said study coauthor Adam G. Sowalsky, Ph.D., instructor in medicine at Harvard Medical School.

The study, published in Oncotarget March 31, was funded by the National Institutes of Health and Department of Defense. Primary authors are Leszek Kotula, M.D., Ph.D., associate professor of urology and biochemistry and molecular biology; and Adam G. Sowalsky, Ph.D., instructor in medicine at Harvard Medical School. Other authors of the study include Dr. Pier Paolo Pandolfi, Dr. Steven Balk, Rachel Schaefer (Harvard Medical School, Boston, MA), and Dr. Gennady Bratslavsky and Rebecca Sager (Upstate Medical University, Syracuse, NY).

The study builds on earlier research (funded by the Department of Defense and the Kirby Foundation, Morristown, N.J.) by Kotula that implicated another gene, ABI1, as a tumor suppressor in prostate cancer. For the Oncotarget study researchers sought to find other genes that cooperate with ABI1 in the progression of prostate cancer, thus finding the WAVE1 gene as a culprit.

Kotula said his lab is now replicating the gene deletion in mice. Such work can aid in the development of drugs or new treatments to suppress tumors or provide more precision in the treatment of these aggressive cancers.

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Researchers Identify Subtype of Lethal Prostate Cancer

Mammal species with higher copy numbers of siglec receptor genes have longer maximum lifespans

We age in part thanks to "friendly fire" from the immune system -- inflammation and chemically active molecules called reactive oxygen species that help fight infection, but also wreak molecular havoc over time, contributing to frailty, disability and disease. The CD33rSiglec family of proteins are known to help protect our cells from becoming inflammatory collateral damage, prompting researchers at the University of California, San Diego School of Medicine to ask whether CD33rSiglecs might help mammals live longer, too.

In a study published April 7 by eLife, the team reports a correlation between CD33rSIGLEC gene copy number and maximum lifespan across 14 mammalian species. In addition, they found that mice lacking one CD33rSIGLEC gene copy don't live as long as normal mice, have higher levels of reactive oxygen species and experience more molecular damage.

"Though not quite definitive, this finding is provocative. As far as we know, it's the first time lifespan has been correlated with simple gene copy number," said Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the UC San Diego Moores Cancer Center. "Since people also vary in number of CD33rSIGLEC gene copies, it will be interesting to see if these genes influence variations in human lifespan as they do in mice."

Varki led the study, along with Pascal Gagneux, PhD, associate professor of pathology.

The CD33rSIGLEC genes encode siglec receptors that bind sialic acids -- sugar molecules found on many cells. These siglec receptors stick out like antennae on the outer surface of immune cells, probing the surface of other "self" cells in the body. When sialic acids bind siglec receptors, they transmit the message to the inside of the cell. This signal relay puts a brake on immune cell activation. In this way, the CD33rSiglec receptors help dampen chronic inflammation and reactive oxygen species in the body.

Different mammal species carry different numbers of the CD33rSIGLEC genes in their genomes. In this study, Varki, Gagneux and colleagues surveyed 14 different mammalian genomes, including those of elephants, dogs, monkeys and humans, and found that CD33rSIGLEC gene number correlates with maximum lifespan. In other words, species with more copies tend to live longer, even when the researchers controlled for other factors, such as body mass, adjacent genes and shared evolutionary history.

To dig deeper, Varki, Gagneux and team turned to a mouse model. They discovered that mice that were missing one CD33rSIGLEC gene and experienced inflammation early in life showed signs of accelerated aging (gray hair, disorientation, thin skin), had higher levels of reactive oxygen species and did not live as long as normal mice.

"The higher CD33rSIGLEC gene number can be thought of as an improved maintenance system that co-evolved in mammals to buffer against the effects of many infectious episodes fought off by the immune system of long-lived mammals," said Gagneux.

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More anti-inflammatory genes mean longer lifespans for mammals