Category Archives: Anti-Aging Medicine

Nutrient found in beef and dairy improves immune response to cancer – EurekAlert

Trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to infiltrate tumors and kill cancer cells, according to a new study by researchers from the University of Chicago.

The research, published this week in Nature, also shows that patients with higher levels of TVA circulating in the blood responded better to immunotherapy, suggesting that it could have potential as a nutritional supplement to complement clinical treatments for cancer.

There are many studies trying to decipher the link between diet and human health, and its very difficult to understand the underlying mechanisms because of the wide variety of foods people eat. But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology, said Jing Chen, PhD, the Janet Davison Rowley Distinguished Service Professor of Medicine at UChicago and one of the senior authors of the new study. By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumor immunity by activating an important immune pathway.

Finding nutrients that activate immune cells

Chens lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence the development of cancer and response to cancer treatments. For the new study, two postdoctoral fellows, Hao Fan, PhD and Siyuan Xia, PhD, both co-first authors, started with a database of around 700 known metabolites that come from food and assembled a blood nutrient compound library consisting of 235 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to influence anti-tumor immunity by activating CD8+ T cells, a group of immune cells critical for killing cancerous or virally infected cells.

After the scientists evaluated the top six candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. That means there must be something else it does, so we started working on it more, Chen said.

The researchers then conducted a series of experiments with cells and mouse models of diverse tumor types. Feeding mice a diet enriched with TVA significantly reduced the tumor growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumors.

The team also performed a series of molecular and genetic analyses to understand how TVA was affecting the T cells. These included a new technique for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, PhD, the John T. Wilson Distinguished Service Professor of Chemistry at UChicago and another senior author of the study. These additional assays, done by both the Chen and He labs, showed that TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota. TVA overpowers these short-chain fatty acids and activates a cellular signaling process known as the CREB pathway, which is involved in a variety of functions including cellular growth, survival, and differentiation. The team also showed that mouse models where the GPR43 receptor was exclusively removed from CD8+ T cells also lacked their improved tumor fighting ability.

Finally, the team also worked with Justin Kline, MD, Professor of Medicine at UChicago, to analyze blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with higher levels of TVA tended to respond to treatment better than those with lower levels. They also tested cell lines from leukemia by working with Wendy Stock, MD, the Anjuli Seth Nayak Professor of Medicine, and saw that TVA enhanced the ability of an immunotherapy drug to kill leukemia cells.

Focus on the nutrients, not the food

The study suggests that TVA could be used as a dietary supplement to help various T cell-based cancer treatments, although Chen points out that it is important to determine the optimized amount of the nutrient itself, not the food source. There is a growing body of evidence about the detrimental health effects of consuming too much red meat and dairy, so this study shouldnt be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutrient supplements such as TVA could be used to promote T cell activity. Chen thinks there may be other nutrients that can do the same.

There is early data showing that other fatty acids from plants signal through a similar receptor, so we believe there is a high possibility that nutrients from plants can do the same thing by activating the CREB pathway as well, he said.

The new research also highlights the promise of this metabolomic approach to understanding how the building blocks of diet affect our health. Chen said his team hopes to build a comprehensive library of nutrients circulating in the blood to understand their impact on immunity and other biological processes like aging.

After millions of years of evolution, there are only a couple hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology, Chen said. To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type, with a very profound physiological response at the whole organism levelI find that really amazing and intriguing.

The study, Trans-vaccenic acid reprograms CD8+ T cells and anti-tumor immunity, was supported by the National Institutes of Health (grants CA140515, CA174786, CA276568, 1375 HG006827, K99ES034084), a UChicago Biological Sciences Division Pilot Project Award, the Ludwig Center at UChicago, the Sigal Fellowship in Immuno-oncology, the Margaret E. Early Medical Research Trust, the AASLD Foundation a Harborview Foundation Gift Fund, and the Howard Hughes Medical Institute.

Experimental study

Animals

Trans-vaccenic acid reprograms CD8+ T cells and anti-tumor immunity

22-Nov-2023

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Nutrient found in beef and dairy improves immune response to cancer - EurekAlert

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Deep Space Astronauts May Be Prone To Erectile Dysfunction … – Slashdot

As if homesickness, wasting muscles, thinner bones, an elevated cancer risk, the inescapable company of overachievers and the prospect of death in the endless vacuum of space were not enough to contend with, male astronauts may return from deep space prone to erectile dysfunction, scientists say. From a report: In what is claimed to be the first study to assess the impact of galactic radiation and weightlessness on male sexual health, Nasa-funded researchers found that galactic cosmic rays, and to a lesser extent microgravity, can impair the function of erectile tissues, with effects lasting potentially for decades. Raising their concerns in a report on Wednesday, the US researchers said they had identified "a new health risk to consider with deep space exploration." They called for the sexual health of astronauts to be closely monitored on their return from future deep space missions, noting that certain antioxidants may help to counteract the ill-effects by blocking harmful biological processes.

"While the negative impacts of galactic cosmic radiation were long-lasting, functional improvements induced by acutely targeting the redox and nitric oxide pathways in the tissues suggest that the erectile dysfunction may be treatable," said Dr Justin La Favor, an expert in neurovascular dysfunction at Florida State University and a senior author on the study. The warning comes amid a renewed focus on deep space missions, with Nasa and other major space agencies preparing for long-term expeditions to the moon and more ambitious voyages to Mars. Nasa's Artemis programme aspires to send astronauts to the moon as early as next year, with crewed missions to Mars tentatively lined up for as early as 2040.

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FDA Considers First CRISPR Gene Editing Treatment That May … – Slashdot

The U.S. Food and Drug Administration is reviewing a cutting-edge therapy called exa-cel that could potentially cure people of sickle cell disease, a painful and deadly disease with no universally successful treatment. "If approved, exa-cel, made by Boston-based Vertex Pharmaceuticals and the Swiss company CRISPR Therapeutics, would be the first FDA-approved treatment that uses genetic modification called CRISPR," reports CNN. From the report: CRISPR, or clustered regularly interspaced short palindromic repeats, is a technology researchers use to selectively modify DNA, the carrier of genetic information that the body uses to function and develop. [...] The new exa-cel treatment under FDA consideration can use the patient's own stem cells. Doctors would alter them with CRISPR to fix the genetic problems that cause sickle cell, and then the altered stem cells are given back to the patient in a one-time infusion.

In company studies, the treatment was considered safe, and it had a "highly positive benefit-risk for patients with severe sickle cell disease," Dr. Stephanie Krogmeier, vice president for global regulatory affairs with Vertex Pharmaceuticals Incorporated, told the panel. Thirty-nine of the 40 people tested with the treatment did not have a single vaso-occlusive crisis, which means the misshapen red blood cells block normal circulation and can cause moderate to severe pain. It's the top reason patients with sickle cell go to the emergency room or are hospitalized. Before the treatment, patients experienced about four of these painful crises a year, resulting in about two weeks in the hospital.

The FDA sought the independent panel's advice, in part, because this would be the first time the FDA would approve a treatment that uses CRISPR technology, but Dr. Fyodor Urnov, a professor in the Department of Molecular and Cell Biology at the University of California, Berkeley, reminded the committee CRISPR has been around for 30 years and, in that time, scientists have learned a lot about how to use it safely. "The technology is, in fact, ready for primetime," Urnov said. With this kind of genetic editing, scientists could inadvertently make a change to a patient's DNA that is off-target, and the therapy could harm the patient. [...] The FDA is expected to make an approval decision by December 8.