Category Archives: Genetic Medicine

In September, the world of entertainment news buzzed with word that Kim Kardashian West tested positive for lupus and rheumatoid arthritis. The star underwent further tests, however, resulting in a diagnosis of psoriatic arthritis instead. While all three autoimmune disorders share some signs and symptoms, psoriatic arthritis is generally considered to have a better prognosis than lupus. That said, the conditions can co-exist and lupus has gotten a reputation for being difficult to diagnose, especially in the absence of the butterfly-shaped rash on ones cheeks and nose.

Im so relieved. The pain is going to come and go sometimes, but I can manage it and this is not going to stop me, Kardashian said in an article in response to receiving her psoriatic arthritis diagnosis. Her relief at not having lupus is understandable, given that lupus can affect a greater number of organs and systems in the body and is considered to be life-threatening.

Lupus, rheumatoid arthritis and psoriatic arthritis are examples of some conditions that are often considered when an individual is undergoing diagnosis for certain autoimmune diseases, because they share several symptoms and can trigger positive results in the same diagnostic tests. Kim Kardashian received the initial news that she had lupus or rheumatoid arthritis likely due to positive antinuclear antibody (ANA) test results.

An ANA is a blood test ordered when a doctor, usually a rheumatologist, suspects that a patient has a particular kind of autoimmune disorder. This test checks for the existence of autoantibodies, which are produced when a persons body is, in effect, attacking itself and several areas of the body are affected. A positive ANA test usually indicates that the doctors suspicions are confirmed, and then other factors (like medical and family history) need to be considered and more tests done to arrive at a diagnosis.

Psoriatic arthritis is usually diagnosed between the ages of 20 and 50, and occurs in women and men equally. While there is no cure, appropriate and early treatment can help prevent major damage to affected parts of the body.

Psoriatic arthritis appears in a minority of individuals who have already been diagnosed with psoriasis, an autoimmune skin condition with which Kim Kardashian and her mother, Kris Jenner, had already been diagnosed. Psoriatic arthritis affects around 520,000 individuals in the United States alone.

The autoimmune condition is believed to be caused by a combination of genetic factors and environmental triggers. So while some people inherit psoriatic arthritis-related genes, only a subset of those individuals will go on to develop the condition. In these cases, the disease could be triggered by other illnesses or infections, various forms of extreme stress, poor diet, smoking, and so on.

Around 40 percent of psoriatic arthritis patients have one or more close family members with psoriasis or psoriatic arthritis diagnosis, which strongly indicates that the disease is hereditary. Interestingly, recent research has suggested that psoriasis patients who go on to develop psoriatic arthritis have a different genetic profile than those who do not. And the most well-studied of the psoriatic arthritis genes belong to a family of genes called the human leukocyte antigen (HLA) complex, which help the body tell the difference between its own proteins and viral or bacterial proteins.

According to Genetics Home Reference by the U.S. National Library of Medicine, Variations of several HLA genes seem to affect the risk of developing psoriatic arthritis, as well as the type, severity, and progression of the condition.

Ive been feeling so tired, so nauseous, and my hands are really getting swollen. I feel like I literally am falling apart. My hands are numb, Kardashian said on a recent episode of Keeping Up with the Kardashians.

These kinds of descriptions are common in all three conditions lupus, rheumatoid arthritis, and psoriatic arthritis though each patient presents with a different array of symptoms, and all with varying degrees of severity. The main symptoms of psoriatic arthritis are pain, stiffness, and swelling in affected joints, along with chronic fatigue. Joints near the end of the fingertips and tips of the toes are often affected, as are bones in the spine.

The symptoms of psoriatic arthritis tend to worsen over time, though some patients experience periods of remission when symptoms temporarily improve. Compared to rheumatoid arthritis, psoriatic arthritis is more likely to cause swelling in the smallest joints of the fingers and toes, foot pain (in the heel and/or sole of the foot), and lower back pain caused by inflammation in vertebral joints. Patients with psoriatic arthritis are also more likely to experience symptoms on one side of the body or in different appendages on each side (in other words, it tends to be an asymmetric disease), whereas patients with rheumatoid arthritis are more likely to experience symptoms that affect both sides of the body equally (symmetric disease).

Most if not all patients with psoriatic arthritis also have psoriasis, an autoimmune condition that causes red, scaly patches of skin that can be itchy, painful and embarrassing. Psoriasis usually precedes the onset of psoriatic arthritis by several years. People with psoriatic arthritis commonly experience fingernail changes, too, such as the formation of a pitted or ridged nail surface, or the nails become separated from the nail beds.

There are several treatment options for psoriatic arthritis, which include nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and pain, immunosuppressants to suppress the immune system, disease-modifying antirheumatic drugs (DMARDs) to slow the progression of the disease, and newer medications that minimize the activity of certain enzymes involved in the inflammatory process. Treatment plans may also involve steroid injections administered directly into affected joints, or joint replacement surgery in cases where the disease has significantly progressed.

Kristen Hovet covers genetics, medical innovations and the intersection of sociology and culture. The North Dakota native is based in Vancouver, Canada, where she is working on a masters degree in health communication at Washington State University. Follow her on her website or Twitter @kristenhovet

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Kim Kardashian West's battle with psoriatic arthritis: Will understanding the genetics of the autoimmune disorder point to a cure? - Genetic Literacy...

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) approved Tecentriq (atezolizumab) in combination with chemotherapy (Abraxane [paclitaxel protein-bound; nab-paclitaxel] and carboplatin) for the initial (first-line) treatment of adults with metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations.

We are pleased to offer this Tecentriq-based combination as a new treatment option that can provide a clinically meaningful survival benefit for people with non-squamous non-small cell lung cancer, said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. Todays approval offers another opportunity to help prolong the lives of people with this type of the disease.

This approval is based on results from the Phase III IMpower130 study, which showed Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (median overall survival [OS] = 18.6 versus 13.9 months; hazard ratio [HR] = 0.80; 95% CI: 0.640.99; p=0.0384) in the intention-to-treat wild-type (ITT-WT) population. The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (progression-free survival; PFS) compared with chemotherapy alone (median PFS=7.2 versus 6.5 months; HR=0.75; 95% CI: 0.630.91; p=0.0024) in the ITT-WT population.

Safety for the Tecentriq plus chemotherapy combination appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination. Grade 3-4 treatment-related adverse events were reported in 73.2% of people receiving Tecentriq plus chemotherapy compared with 60.3% of people receiving chemotherapy alone.

In lung cancer, Tecentriq is also approved in combination with Avastin (bevacizumab), paclitaxel and carboplatin (chemotherapy), for the initial (first-line) treatment of adults with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. Additionally, Tecentriq is approved by the FDA to treat adults with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving Tecentriq. Tecentriq is also approved in combination with carboplatin and etoposide (chemotherapy) for the initial (first-line) treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).

Genentech has an extensive development program for Tecentriq, including nine Phase III studies underway across different types of lung cancer, and multiple ongoing and planned Phase III studies across genitourinary, skin, breast, gastrointestinal, gynecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

For those who qualify, Genentech offers patient assistance programs for people taking Tecentriq through Genentech Access Solutions. Doctors can contact Genentech Access Solutions at (866) 422-2377. More information is also available at http://www.Genentech-Access.com.

About the IMpower130 study

IMpower130 is a Phase III, multicenter, open-label, randomized study evaluating the efficacy and safety of Tecentriq in combination nab-paclitaxel and carboplatin versus chemotherapy (nab-paclitaxel and carboplatin) alone for chemotherapy-nave patients with stage IV non-squamous NSCLC. The study enrolled 724 people, of whom 681 were in the ITT-WT population and were randomized (2:1) to receive:

During the treatment-induction phase, people in Arm A received Tecentriq and carboplatin on day 1 of each 21-day cycle, and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit, whichever occurred first. People in Arm A received Tecentriq during the maintenance treatment phase until loss of clinical benefit was observed.

During the treatment-induction phase, people in Arm B received carboplatin on day 1 and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression, whichever occurred first. People in Arm B received best supportive care during the maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. People who were consented prior to a protocol revision were given the option to crossover to receive Tecentriq as monotherapy until further disease progression.

The co-primary endpoints were:

About lung cancer

According to the American Cancer Society, it is estimated that more than 228,000 Americans will be diagnosed with lung cancer in 2019, and NSCLC accounts for 80-85% of all lung cancers. It is estimated that approximately 60% of lung cancer diagnoses in the United States are made when the disease is in the advanced stages.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Abraxane is a registered trademark of Abraxis Bioscience, LLC, a wholly owned subsidiary of Celgene Corporation.

Tecentriq U.S. Indications

Tecentriq is a prescription medicine used to treat adults with:

A type of lung cancer called non-small cell lung cancer (NSCLC).

A type of lung cancer called small cell lung cancer (SCLC).

It is not known if Tecentriq is safe and effective in children.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.Tecentriq.com for the Tecentriq full Prescribing Information for additional Important Safety Information.

About Genentech in personalized cancer immunotherapy

For more than 30 years, Genentech has been developing medicines with the goal to redefine treatment in oncology. Today, were investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer. The goal of PCI is to provide each person with a treatment tailored to harness his or her own immune system to fight cancer. Genentech is studying more than 10 cancer immunotherapy medicines across 70 clinical trials alone or in combination with other medicines. In every study we are evaluating biomarkers to identify which people may be appropriate candidates for our medicines. For more information visit http://www.gene.com/cancer-immunotherapy.

About Genentech in lung cancer

Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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FDA Approves Genentech's Tecentriq Plus Chemotherapy (Abraxane and Carboplatin) for the Initial Treatment of Metastatic Non-Squamous Non-Small Cell...

Rapid advances in telomere biology are paving the way to new clinical applications that promise better diagnosis and treatment options in select patients. Scientists understanding about the role of telomerescaps at the ends of chromosomes that prevent attrition of DNAhas progressed to the point that telomere measurements are being used in diagnostic workups at some medical centers. Broader dissemination of this type of analysis will go hand-in-hand not only with a deeper understanding of the link between telomere length and health and disease but also more standardized testing methods and parameters. Expanding the use of telomere testing also will depend on better coordinated care among clinical disciplines that have not traditionally worked together, according to Mary Armanios, MD, professor of oncology, genetic medicine, molecular biology and genetics, and pathology at Johns Hopkins University in Baltimore.

The causal role telomeres play in aging and age-related diseases has been known for decades. However, new studies now reveal that extreme short or long telomere lengths are associated with specific heritable diseases and cancers. This knowledge, a pivotal advance, has added urgency to the quest to accurately measure telomere length and define clinically relevant short and long thresholds. With the advent of precision genomics, we have the opportunity to identify and manage these disorders for the benefit of patients, said Mrinal Patnaik, MBBS, an associate professor of medicine and oncology and a consultant hematologist at the Mayo Clinic in Rochester, Minnesota.

Telomeres shorten every time a cell divides, naturally shortening with age and at a certain point signaling cells to stop dividing and become senescent. However, when genes responsible for telomere synthesis, trafficking, maintenance, and for telomerase function are perturbed, accelerated telomere shortening leads to a group of genetic disorders called short telomere syndromes (STS). Notably, although 13 causative genes have been identified, these account for only about 40% of STS cases. The fact that more than half of our patients with short telomeres do not have detectable gene mutations on sequencing panels indicates that we havent yet discovered all the mutations that affect telomere length, said Patnaik.

STS encompass disparate clinical manifestations across multiple organ systems including immunodeficiency, idiopathic pulmonary fibrosis and emphysema, esophageal stenosis and enterocolitis, hepatic fibrosis and cirrhosis, and bone marrow failure. Anytime you see a triad of symptoms that include premature greying of hair, fibrotic involvement of lung and liver, and bone marrow failure, it should raise flags as a potential STS, said Patnaik.

In contrast, mutations that lengthen telomeres cause long telomere syndromes. These are associated with a high cancer risk: glioma and familial melanoma, in particular. Insights from genome-wide association studies have identified genetic variants in telomere-related genes concurrent with these cancers, further strengthening the telomere-cancer link.

Diagnosing patients with telomere length disorders is challenging, especially STS, given their broad clinical spectrum. The Telomere Clinic at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, which Armanios leads, offers a telomere measurement service to clinicians and provides multidisciplinary care to patients with telomere-related disorders. Our goal was to establish a clinically reliable tool for telomere length measurement in a hospital setting and make it available to physicians and their patients for precise diagnosis and treatment recommendations, she said.

Patients with severe STS often need organ transplants as a result of end-organ failure. Telomere-related testing can offer these patients a more tailored approach to managing their disease, especially in pre-transplant settings. For example, most patients with STS cant tolerate standard doses of radiation and cytotoxic therapies; recognizing this enables physicians to choose a different conditioning regimen. Also, dysfunctional telomere-related gene(s) are passed through autosomal or X-linked transmission; physicians can therefore screen potential donorsoften patients close relativesto make sure they do not carry these same faulty gene(s).

Armanios and her team recently reported using telomere length as a diagnostic tool to identify patients with STS (Proc Natl Acad Sci U S A 2018;115:E235865). After establishing normal telomere ranges from a healthy control population and determining that telomere measurements have tight concordance and reproducible upper and lower boundaries across populations, they also found that most patients with variants in telomere-related genes had short telomere lengths. In addition, they observed a correlation between the severity of the disease phenotype and the age at diagnosis. We saw different clinical presentations depending on when telomeres reached a critical threshold, said lead author Jonathan Alder, PhD, now an assistant professor of medicine at the University of Pittsburgh. Crucially, the Johns Hopkins team reported that telomere measurements led to treatment changes in one-quarter of 38 pediatric and adult patients with idiopathic bone marrow failure as physicians changed to less harsh therapies like reduced doses of chemotherapy and less use of immunosuppressant drugs.

Patnaik and his colleagues also use telomere testing to assess patients with bone marrow failure, as part of Mayo Clinics Center for Individualized Medicine. We found very quickly that the most common referrals to the Center were people with short telomere syndromes that extended beyond bone marrow failure into conditions like lung and liver fibrosis, he said. In recent reports, he and his team have described their diagnostic workups for patients with suspected inherited STS and with unexplained cytopenias. In the case of inherited STS, they defined this population as having telomere lengths in either granulocytes or lymphocytes less than the first centile of normal controls (Mayo Clin Proc 2018;93:834-9). They perform this screening in concert with an in-house next-generation-sequencing (NGS) panel that consists of telomere-associated genes. Patients who test negative for the NGS panel proceed to research-based whole-exome sequencing to identify other potential mutations.

The options for measuring telomere length are broadand complicated. We are measuring a population of cells, and each cell has between 92 and 184 telomeres, so we are really measuring a population of telomere lengths in an individual, said Alder. Some methods measure individual telomere length, some measure the average, some measure the average of many cells together, and still others measure the average of individual cells.

These methodologies encompass quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH)-based techniquesincluding flow cytometry combined with FISH (flow-FISH) and quantitative FISHtelomere restriction fragment length analysis, optical techniques, and hybridization protection assays. In hospital settings, the preferred method is flow-FISH, which both Johns Hopkins and Mayo Clinic use. Both favor this approach because of its accuracy, reproducibility, ability to define normal telomere length range, and ability to test large numbers of samples. Flow-FISH is standardized, clinically validated, cost-effective, commercially available, and can be implemented anywhere to screen patients with suboptimal telomere length, said Patnaik. Flow-FISH reports also provide data on telomere lengths relative to age, which is important because telomere attrition is part of the normal aging process.

Although an estimated 5,000 to 10,000 individuals in the U.S. have STS, the place for telomere testing remains unclear in diagnosing and predicting long telomere-associated cancers. In cancers where telomere length is elongated, the role of telomere-related testing is still ongoing and not quite ready for clinical prime time, said Patnaik. He added that more research into understanding why shorter telomeres negatively impact outcomes in the management of bone marrow failure syndromes and blood cancers will be quite useful, potentially informing future clinical interventions.

Others remain skeptical about how broadly telomere testing might disseminate. Telomere length testing makes complete sense for rare diseases like STS where you have a specific genetic cause. But I dont think it has any clinical relevance as yet for identifying risk factors for more common diseases like cancer, cardiovascular disease, diabetes, chronic lung disease, Alzheimers disease, and infectious diseases, said Brge Nordestgaard, MD, professor of clinical medicine at the University of Copenhagen and chief physician in the department of clinical biochemistry at Herlev and Gentofte Hospital and Copenhagen University Hospital Denmark. Nordestgaard has conducted genetic epidemiology studies exploring long telomere length and cancer risk and short telomere length and ischemic heart disease risk.

Alder agreed that work remains in identifying the best diagnostic niches for this emerging field. Telomere testing is definitely not a standard part of every clinical work-up in the nation. In the future, it is important to define clinical scenarios where it makes sense for telomeres to be measured, he said. The next step would be to define what the critical thresholds are for making a diagnosis that can lead to an actionable intervention.

Even as the science and practice of telomere testing remains in flux, Armanios, speaking at a Pulmonary Fibrosis Foundation meeting, laid out a future in which genetic evaluation with telomere length might replace lung biopsies in affected patients. She also envisions a time when identifying patients with telomere-mediated lung disease could aid in managing lung transplants, both for anticipating and averting complications.

One catch in advancing the field is that there are no specific treatments for telomere biology disorders. Patnaik echoed Armanios call for specialty-crossing care to plot next steps for newly diagnosed patients. More centers of excellence are needed that can integrate different clinical fields and provide a unique multidisciplinary skill set to manage and counsel these patients, he stressed.

Pranali P. Pathare, PhD, is a medical writer and editor in St. Louis. +Email: ppranali@gmail.com

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On the Trail of Telomeres - American Association for Clinical Chemistry (AACC)

With any addiction in which a user has successfully resisted a chemical, activity or substance, relapse is vexing. And with opioids, its often deadly. Fatal overdoses following relapse from an opioid addiction is reaching epidemic proportions.

In 2017, more than 70,000 people died from drug overdoses, making it a leading cause of injury-related death in the United States, according to the Centers for Disease Control and Prevention. Of those deaths, almost 68 percent involved a prescription or illicit opioid.

A study published in Neuropsychopharmacology reported that relapse can be prevented by controlling cells in a brain region called the nucleus accumbens. The study was conducted among 90 Sprague Dawley rats with genetic diversity.

We used a tool called chemogenetic receptors to act as a light switch on the cells, said senior author Susan Ferguson, director of the Alcohol and Drug Abuse Institute at the University of Washington and associate professor of psychiatry and behavioral sciences at UWs School of Medicine. When we changed activity of neurons in the nucleus accumbens, we were able to control relapse behavior.

She said this process could be used to prevent relapse for any addiction including compulsive gambling and overeating because they affect the same brain regions as drug addiction.

Among the 90 rats exposed to heroin, roughly 40% developed addiction-like behavior. The researchers used six common features of addiction to determine whether the rats were high-risk or casual users:

With this model, the researchers focused on identifying the brain circuitry that regulates addictive behavior, and used artificial receptors to control activity in the nucleus accumbens. Receptors are activated by chemicals such as dopamine or by medications, which cause brain cell activity to increase or decrease.

The researchers could affect the behavior only of the high-risk rats, however, and they could not discern what motivated some rats to use drugs and others to ignore the drugs. Future studies could explore that, Ferguson said.

The research confirms the influence of chemogenetic receptors, Ferguson said, and shows how technology can target specific cell populations in the brain rather than the entire brain.

I envision and hope we could make a pill that decreases relapse but still keeps people motivated for other things, and feeling good, she said.

Funding for the study came fromthe National Institute on Drug Abuse and theNational Institute of Neurological Disorders.

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Researchers find clue to preventing addiction relapse - UW Medicine Newsroom

Early research supports the theory that humans age as a result of primeval genetic mechanisms intended to regulate and repair our aging cells. But could there be ways to "turn off" these mechanisms to slow or even reverse aging? David Sinclair and Matthew LaPlante dig into the science in the Wall Street Journal.

The best resources to guide your precision medicine strategy

New developments in the field of epigenetics are changing our understanding of the genetic underpinnings of aging.

Sinclair, a professor of genetics at Harvard Medical School, and LaPlante, an associate professor of journalism at Utah State University, describe epigenetics using the metaphor of a piano. "If you think of your inherited genetics, your DNA, as a piano keyboard, then epigenetics determines how the keys play music," they write. "The primary players in this concert are molecular substances that affix to our genome and leave markers."

These epigenetic markers determine how genes functionessentially turning them "on" and "off" and they are a crucial way that our bodies regulate themselves. However, as numerous markers accumulate over time, they can create "epigenetic noise," as Sinclair and LaPlante write, which can cause cells to become dysfunctional.

Researchers have discovered in recent years that the number of epigenetic markers acting on a person's cells can provide a surprisingly accurate measurement of his or her age. Now, a new "information theory" is growing in prominence, claiming that epigenetic markers may not just help us measure agebut that they may actually cause the decay associated with the aging process.

Essentially, once a cell suffers from too much epigenetic noise, the theory claims, it becomes senescent and stops reproducing. This has a cascading effect on all adjacent cells, Sinclair and LaPlante write, causing the proliferation of symptoms that we associate with aging.

Elements of this theory have been demonstrated in research on mice. When Harvard Medical School researchers altered young mice's genomes by adding epigenetic accretions, the mice experienced accelerated muscle and bone mass loss, began turning gray, experienced vision problems, and became more easily confused. In essence, they physically got older, even when they were chronologically still young.

Epigenetic mechanisms evolved in some of the earliest life forms on earth to regulate and repair cells that aren't functioning properly. However, if the information theory is true, these same mechanisms are paradoxically what cause us to suffer from aging.

"[T]here is no law of biology that says we must age at the rate at which we do now," Sinclair and LaPlante write, adding that some other forms of life don't age like humans do. For instance, the bristlecone pine doesn't appear to experience aging and can survive for 5,000 years.

Even in humans, some portion of our epigenetic markers are due to unhealthy behaviors, such as a poor diet or overexposure to the sun. While ending these behaviors will slow deterioration, scientists believe there may be other ways to "reboot" a cell to fight, or even reverse, cellular aging.

In a 2016 study published in Cell, researchers at the Salk Institute in San Diego found they could extend the lifespans of mice suffering from premature aging by almost a third. The trick? They transiently turned on four genes that can eliminate accumulated epigenetic markers and induce "pluripotency," or the ability of a cell to develop into other adult cell forms, Sinclair and LaPlante write.

Similarly, researchers at Harvard found that giving elderly, blind mice a combination of three genes over three weeks, and then turning on these genes using epigenetic markers, rejuvenated their optic nerves and restored their vision.

Sinclair, together with Juan Carlos Belmonte from the Salk Institute and Steven Horvath at UCLA, has developed a company aiming to develop medicines for eye diseases based on their research. However, Sinclair and LaPlante caution that "there is a great distance between what can be done with mice in a lab and what can be done to help humans fight diseases and extend their healthy years."

Sinclair and LaPlante also write that "healthy" is the operative term. "You would be hard-pressed to find anyone who thinks it would be a good idea to lengthen human lives if we cannot substantially improve the part of life that is lived free of debilitating diseases," they write.

Their early work in humans holds some promise. The researchers published a small study in which they gave nine patients a mix of three molecules: growth hormone; DHEA, a steroid; and metformin, an anti-diabetic medication that has been shown in preliminary research to slow cellular aging. They found that the patients experienced an epigenetic age reversal, losing two years off of the biological ages of their cells.

Sinclair and LaPlante write that there was no control group, and the results should be considered preliminary until larger, more rigorous studies take place. "But it is no longer completely crazy to talk about having birthdays in reverse," they write (Sinclair/LaPlante, Wall Street Journal, 10/25).

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Do we have to age and die? Here's what science says. - The Daily Briefing

Results of a new study in mice suggest that the body may be able to defeat the influenza virus if a person has the right sort of diet a ketogenic, or keto, diet.

Infection with the influenza virus, better known as the flu, has accounted for 12,00061,000 deaths every year since 2010 in the United States, with an annual economic burden of $87.1 billion.

The introduction of the flu vaccine has greatly improved infection and morbidity rates. However, there is still currently no cure for the illness.

Healthcare professionals and scientists alike are continuing the search for novel therapeutics to combat the flu, yet the key may lie within the body's own immune system. Moreover, it may be activated by the keto diet.

Following the keto diet involves eating foods that are high in fat and low in carbohydrates. Meals tend to consist of a variety of meat, fish, poultry, and non-starchy vegetables.

According to the findings of a new study, appearing in the journal Science Immunology, when mice fed a keto diet were injected with the flu virus, their survival rates were much higher than those of mice fed a diet high in carbohydrates.

The main reason for this, the researchers believe, is that a keto diet blocks the formation of inflammasomes, which are multiunit protein complexes that the immune system activates.

Inflammasomes can also cause harmful immune system responses in the host. This triggers the release of gamma delta T cells.

Gamma delta T cells are responsible for producing mucus in the linings of the lungs, which helps the body get rid of infectious agents. The mucus is then wafted up the airways and coughed out.

The joint senior authors of the study are Prof. Akiko Iwasaki and Prof. Vishwa Deep Dixit, both of the department of immunobiology at the Yale School of Medicine, in New Haven, CT.

The objective of the study was to determine how the keto diet affects host defense against a lethal flu virus infection.

The researchers randomly assigned the mice to diet groups 1 week before they induced the infection. Next, they monitored the rodents for signs of infection and assessed their immune responses.

The team found that keto diet feeding confers protection against the flu virus in mice by increasing the number of gamma delta T cells in the airways.

This response occurred relatively late after the infection in the mice, due to their dependence on T cell receptors on other cells. But in humans, this response is much quicker, as gamma delta T cells can expand independently.

In addition, previous research in mice has shown that a specific subset of gamma delta T cells can efficiently induce the cytolytic killing of flu-infected airway cells.

In the current study, the expansion of gamma delta T cells resulted in lower viral titer measurements in the mice that had received a ketogenic diet.

The team also investigated the potential for changes in the levels of genetic activity using RNA sequencing, a technique that can measure the levels of transcription across the genome.

This showed that although a keto diet could impact the expansion of gamma delta T cells, this was not associated with any changes in the activity of genes involved with cytotoxicity.

Interestingly, when mice were bred without the gene that encodes for gamma delta T cells, the keto diet provided no protection against the flu virus.

Commenting on this result, Prof. Iwasaki says, "This was a totally unexpected finding."

"This study shows that the way the body burns fat to produce ketone bodies from the food we eat can fuel the immune system to fight flu infection."

Prof. Vishwa Deep Dixit

How do gamma delta T cells protect the host in response to a keto diet? As the researchers report, the current theory is that the expansion of these cells in response to ketogenic feeding leads to more efficient killing of the flu virus.

This, in turn, results in much lower viral titers and better preservation of the cells lining the airways.

Experts believe that the gamma delta T cells induced by the keto diet may enhance the barrier and innate defense systems of airway-lining cells at baseline, thereby allowing for a better response to the flu virus.

These results demonstrate that the answer to combatting the flu virus does not necessarily lie in producing drugs to relieve flu symptoms and that changing the diet can have a dramatic effect on how the body responds to infection.

The results also suggest that if the flu can be tackled in this way, there is the potential for changes in diet to help the body more effectively fight other viral infections.

This type of research is in its infancy, and much more will be needed to elucidate exactly how the keto diet may help combat the flu.

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Can the keto diet help beat the flu? - Medical News Today