Publisher Health

Living a long, healthy life is everyone’s wish, but it is not an easy one to achieve. Many aging studies are developing strategies to increase health spans, the period of life spent with good health, without chronic diseases and disabilities. Researchers at KAIST presented new insights for improving the health span by just regulating the activity of a protein.
A research group under Professor Seung-Jae V. Lee from the Department of Biological Sciences identified a single amino acid change in the tumor suppressor protein phosphatase and tensin homolog (PTEN) that dramatically extends healthy periods while maintaining longevity. This study highlights the importance of the well-conserved tumor suppressor protein PTEN in health span regulation, which can be targeted to develop therapies for promoting healthy longevity in humans. The research was published in Nature Communications on September 24, 2021.
Insulin and insulin-like growth factor-1 (IGF-1) signaling (IIS) is one of the evolutionarily conserved aging-modulatory pathways present in life forms ranging from tiny roundworms to humans. The proper reduction of IIS leads to longevity in animals but often causes defects in multiple health parameters including impaired motility, reproduction, and growth.
The research team found that a specific amino acid change in the PTEN protein improves health status while retaining the longevity conferred by reduced IIS. They used the roundworm C. elegans, an excellent model animal that has been widely used for aging research, mainly because of its very short normal lifespan of about two to three weeks. The PTEN protein is a phosphatase that removes phosphate from lipids as well as proteins. Interestingly, the newly identified amino acid change delicately recalibrated the IIS by partially maintaining protein phosphatase activity while reducing lipid phosphatase activity.
As a result, the amino acid change in the PTEN protein maintained the activity of the longevity-promoting transcription factor Forkhead Box O (FOXO) protein while restricting the detrimental upregulation of another transcription factor, NRF2, leading to long and healthy life in animals with reduced IIS.
Professor Lee said, “Our study raises the exciting possibility of simultaneously promoting longevity and health in humans by slightly tweaking the activity of one protein, PTEN.” This work was supported by the MInistry of Science and ICT through the National Research Foundation of Korea.
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Materials provided by The Korea Advanced Institute of Science and Technology (KAIST). Note: Content may be edited for style and length.

The intestine is essential for maintaining our energy balance and is a master at reacting quickly to changes in nutrition and nutrient balance. It manages to do this with the help of intestinal cells that among other things are specialized in the absorption of food components or the secretion of hormones. In adult humans, the intestinal cells regenerate every five to seven days. The ability to constantly renew and develop all types of intestinal cells from intestinal stem cells is crucial for the natural adaptability of the digestive system. However, a long-term diet high in sugar and fat disrupts this adaptation and can contribute to the development of obesity, type 2 diabetes, and gastrointestinal cancer.
The molecular mechanisms behind this maladaptation are part of the research field of Heiko Lickert and his group at Helmholtz Munich and the Technical University of Munich. The scientists assume that intestinal stem cells play a special role in maladaptation. Using a mouse model, the researchers investigated the effects of a high-sugar and high-fat diet and compared it with a control group.
From high-calorie diet to increased risk of gastrointestinal cancer
“The first thing we noticed was that the small intestine increases greatly in size on the high-calorie diet,” says study leader Anika Böttcher. “Together with Fabian Theis’ team of computational biologists at Helmholtz Munich, we then profiled 27,000 intestinal cells from control diet and high fat/high sugar diet-fed mice. Using new machine learning techniques, we thus found that intestinal stem cells divide and differentiate significantly faster in the mice on an unhealthy diet.” The researchers hypothesize that this is due to an upregulation of the relevant signaling pathways, which is associated with an acceleration of tumor growth in many cancers. “This could be an important link: Diet influences metabolic signaling, which leads to excessive growth of intestinal stem cells and ultimately to an increased risk of gastrointestinal cancer,” says Böttcher.
With the help of this high-resolution technique, the researchers have also been able to study rare cell types in the intestine, for example, hormone-secreting cells. Among their findings, they were able to show that an unhealthy diet leads to a reduction in serotonin-producing cells in the intestine. This can result in intestinal inertia (typical of diabetes mellitus) or increased appetite. Furthermore, the study showed that the absorbing cells adapt to the high-fat diet, and their functionality increases, thus directly promoting weight gain.
Important basic research for non-invasive therapies
These and other findings from the study lead to a new understanding of disease mechanisms associated with a high-calorie diet. “What we have found out is of crucial importance for developing alternative non-invasive therapies,” says study leader Heiko Lickert, in summarizing the results. To date, there is no pharmacological approach to prevent, stop or reverse obesity and diabetes. Only bariatric surgery causes permanent weight loss and can even lead to remission of diabetes. However, these surgeries are invasive, non-reversible and costly to the healthcare system. Novel non-invasive therapies could happen, for example, at the hormonal level through targeted regulation of serotonin levels. The research group will examine this and other approaches in subsequent studies.

An unborn baby could become infected with Covid-19 if their gut is exposed to the SARS-CoV-2 virus, finds a new study led by UCL researchers with Great Ormond Street Hospital for Children and the NIHR Great Ormond Street Biomedical Research Centre.
Although the study did not look specifically at mothers with Covid-19 and whether their infection was transmitted to an unborn baby, it found that certain fetal organs, such as the intestine, are more susceptible to infection than others.
However, researchers say, that opportunities for the Covid-19 virus infecting the fetus are extremely limited, as the placenta acts as a highly effective and protective shield, and evidence suggests fetal infection, known as vertical transmission, is extremely uncommon.
For the study, published in BJOG — An International Journal of Obstetrics & Gynaecology, researchers set out to understand how newborn babies could have developed Covid-19 antibodies, as has been reported in a small number of cases.
Specifically, they wanted to know if and how the virus could be passed from an infected mother to the unborn fetus.
To answer this question, researchers examined various fetal organs and placenta tissue to see if there was any presence of the cell surface protein receptors, ACE2 and TMPRSS2. These two receptors sit on the outside of cells and both are needed for the SARS-Cov-2 virus to infect and spread.

A plant-based antiviral, recently discovered by scientists at the University of Nottingham, has been found to be just as effective at treating all variants of the virus SARS-CoV-2, even the highly infectious Delta variant.
The struggle to control the Covid-19 pandemic is made more difficult by the continual emergence of virulent SARS-CoV-2 variants, which are either more infectious, cause more severe infection, or both.
In a new study published in Virulence, a group of scientists, led by Professor Kin-Chow Chang from the School of Veterinary Medicine and Science at the University, found that the Delta variant, compared with other recent variants, showed the highest ability to multiply in cells, and was most able to directly spread to neighbouring cells. In co-infections with two different SARS-CoV-2 variants, the Delta variant also boosted the multiplication of its co-infected partners.
The study also showed that a novel natural antiviral called thapsigargin (TG), recently discovered by the same group of scientists to block other viruses, including the original SARS-CoV-2, was just as effective at treating all of the newer SARS-CoV-2 variants, including the Delta variant.
In their previous studies* the team showed that the plant-derived antiviral, at small doses, triggers a highly effective broad-spectrum host-centred antiviral innate immune response against three major types of human respiratory viruses, including SARS-CoV-2.
In this latest study, the team set out to find out how well the emergent Alpha, Beta and Delta variants of SARS-CoV-2 are able to multiply in cells relative to each other as single variant infections and in co-infections- where cells are infected with two variants at the same time. The team also wanted to know just how effective TG was at blocking these emergent variants.

Riluzole, a drug approved to treat amyotrophic lateral sclerosis (ALS), a disease affecting nerve cells controlling movement, could slow the gradual loss of a particular brain cell that occurs in Niemann-Pick disease type C1 (NPC1), a rare genetic disorder affecting children and adolescents, suggests a study in mice by scientists at the National Institutes of Health.
The study was conducted by Forbes D. Porter, M.D., Ph.D., of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and colleagues in the National Human Genome Research Institute and National Institute of Arthritis and Musculoskeletal and Skin Disease. It appears in Molecular Genetics and Metabolism. The study was supported in part by a grant from the Ara Parseghian Medical Research Foundation.
NPC1 results from an impaired ability to move cholesterol through cells, leading to difficulty controlling movements, liver and lung disease, impaired swallowing, intellectual decline and death. Much of the movement difficulties in NPC1 result from gradual loss of brain cells known as Purkinje neurons. The researchers found that mice with a form of NPC1 have a diminished ability to lower levels of glutamate — a brain chemical that stimulates neurons — after it has bound to a neuron’s surface. High levels of glutamate can be toxic to cells. The researchers believe the buildup of glutamate contributes to the brain cell loss seen in the disease. Riluzole blocks the release of glutamate and hence delays the progression of ALS in people.
In the current study, mice with NPC1 survived 12% longer when treated with riluzole, compared to untreated mice. The researchers believe that riluzole or similar drugs may provide a way to slow disease progression in patients with NPC1.
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Materials provided by NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development. Note: Content may be edited for style and length.

Bacteria generally have a bad reputation, as people first think of certain strains that can cause serious illnesses like pneumonia or meningitis. However, there are many helpful bacteria, known as probiotics, that assist the body in different ways.
University of Cincinnati researchers have now engineered a probiotic designed to target and break down cancer cell defenses, giving therapies an easier way inside to kill tumors. The findings were recently published in the journal Advanced Healthcare Materials.
Nalinikanth Kotagiri, PhD, the senior author of this study, an assistant professor in UC’s James L. Winkle College of Pharmacy and a UC Cancer Center member, studies “solid cancers” or those defined as abnormal cellular growths in “solid” organs such as the breast or prostate, as opposed to leukemia, a cancer affecting the blood. Kotagiri explains many solid cancers have an extracellular matrix made up of collagen and hyaluronic acid. The matrix forms a barrier around the cells and makes it harder for antibodies and immune cells to reach the tumors.
Shindu Thomas, the first author of this study and a graduate student in the Kotagiri lab, worked with E. coli Nissle, a bacteria that has been used as a probiotic for around 100 years and is different from E. coli strains that cause sickness. Through new technology, any protein or enzyme can be manufactured on the E. coli Nissle bacteria.
In this case, the bacteria was engineered to secrete an abundance of smaller structures called outer membrane vesicles on the outer edge of cells. The vesicles carry the same materials present on the bacteria itself, so researchers designed the bacteria to carry an enzyme that breaks down cancers’ extracellular matrix.
Kotagiri said bacteria tend to thrive in low-oxygen and immunodeficient environments, two characteristics found in solid cancers. Because of this, the specially designed bacteria are naturally drawn to these cancers.

Widely accepted myths that urbanization negatively impacts food and land use biodiversity are incorrect, according to a team of researchers who developed a framework for evaluating this intersection. Their results could also affect nutrition and food insecurity in urban areas.
More than 50% of humanity currently lives in urban areas and by 2050 this will grow to 68%. Growing urbanization drives changes in climate, land use, biodiversity and the human diet, according to the researchers.
“We can’t simply assume that urbanization exclusively, negatively impacts food biodiversity,” said Karl S. Zimmerer, E. Willard and Ruby S. Miller Professor of Environment and Society Geography, Penn State, who directs the GeoSyntheSES Lab.
The framework, which was published today (Nov. 19) in One Earth, looks at the intersection of urbanization and agrobiodiversity — biodiversity in food production and consumption as well as agricultural ecosystems — in four different areas: land use; supply chains; food access and foodways; and urban infrastructure and food retail.
Looking at urban and peri-urban land use, there are a wide variety of approaches that help food and nutritional biodiversity. On a city’s fringe, crop land, orchards and dairy farms can supply a range of products.
According to the researchers some U.S. metropolitan areas could become locally self-sufficient in eggs and milk, but only 12% and 16% in fruits and vegetables, respectively. However, in Hanoi, Viet Nam, urban and peri-urban agriculture provides 62% to 83% of vegetables and significant levels of pork and fish. Within a city, and peri-urban area gardens and farms of all sizes, whether they are public or private, roof top or pocket, add to the diversity of food available to residents.

As widely-anticipated decisions about COVID-19 vaccine boosters roll out from U.S. agencies today, insights from an independent study underscore why boosters are important for all adults.
Antibody levels after receiving the Pfizer-BioNTech COVID-19 vaccine vary by age and sex, but across the board, antibody levels dropped significantly within six months, according to an ongoing study led by Texas Biomedical Research Institute (Texas Biomed) and the University of Verona in Italy.
The study found total antibody levels against SARS-CoV-2 varied between age groups and between men and women. Specifically, individuals under the age of 65 had more than twice the level of antibodies than individuals 65 years and older throughout the six months following vaccination. Women had higher antibody levels than men, especially women under the age of 65. Importantly, however, by the six-month mark, antibody levels had decreased by more than 50% from peak levels for everyone in the study.
“While we see how well vaccines have helped keep people out of the hospital and prevent life-threatening disease, antibody levels are quickly declining in all persons regardless of age and sex,” says Brandon Michael Henry, MD, a physician scientist and postdoctoral researcher at Texas Biomed who co-led the study with collaborators in Italy. “Our study provides additional evidence that booster shots for all adults will be important to keep antibody levels up so we can continue to mount an effective immune response against COVID-19 infection and prevent COVID-19 fatalities.”
The findings are based on a group of 787 healthcare workers in Verona, Italy who received two doses of the Pfizer-BioNTech COVID-19 vaccine. They ranged in age from 21 to 75. Their antibody levels were measured before vaccination, after the second dose, and at one, three and six months after the second shot. Henry presented the research at the 9th annual Vaccine Development Center of San Antonio Conference on Nov. 11. The paper has been accepted for publication in the Journal of Medical Biochemistry (preprint here).
Henry and collaborators theorize that the significant sex differences have to do with hormones. Testosterone, which is higher in men, naturally suppresses the immune system, whereas estrogen, which is higher in women, is known to amplify immune responses. Also, some genes that code for certain immune proteins are on the X chromosome, and since women have two X chromosomes, this might help increase immune activity.
“Normally, only one X chromosome is active and the other is mostly deactivated, but there is evidence that immune-related genes stay active on that redundant chromosome and help boost immune responses in women,” Henry says.
However, women, regardless of age, still saw their antibody levels drop by more than 50% from the peak by six months post vaccination.
Henry has also led systematic reviews that show similar results for age and gender. He and colleagues developed a method to standardize research results for antibody levels, by looking at the percentage change in antibody levels, across 32 studies encompassing more than 5,000 people.
“We have observed throughout the pandemic more older people and men suffer the worst consequences of COVID-19,” Henry says. “These studies point to weaker immune responses against SARS-CoV-2 as a contributing factor to this phenomenon.”
Henry stressed that the decline in antibody level does not mean that the vaccines are not effective. Different types of antibodies play different roles in preventing a mild breakthrough infection versus severe disease. The antibodies that help prevent severe disease appear to continue to be effective in most groups even if present at a lower level, which is why vaccination is important. However, as these antibodies will continue to decline with time, booster doses can help maintain adequate levels of these lifesaving antibodies.
On Friday, Nov. 19, the U.S. Food and Drug Administration (FDA) approved boosters for all adults. The Centers for Disease Control and Prevention (CDC) is expected to issue its formal recommendation soon. Previously, the FDA and CDC approved and recommended boosters for certain groups of people. Several states have already moved forward with offering boosters for all adults six months after vaccination.

People who received two doses of the Pfizer COVID-19 vaccine while on TNF inhibitors — a class of immunosuppressants used to treat rheumatoid arthritis and other autoimmune conditions — generated less powerful and shorter-lived antibodies against the virus that causes COVID-19 than healthy people and those on other kinds of immunosuppressants, according to a study by researchers at Washington University School of Medicine in St. Louis. The scientists found this was especially apparent regarding the virus’s delta variant.
The good news is that a third vaccine dose drove antibody levels back up, but the researchers don’t yet know how long the levels will stay high. The findings, available online in Med, a Cell Press journal, suggest that people taking TNF inhibitors face a particularly high risk of breakthrough infections and would benefit most from a third dose.
TNF inhibitors are used to treat autoimmune conditions such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. The class includes medications such as etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi).
“Not all antibodies are equally good at fighting viruses,” said senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine and a professor of molecular microbiology and of pathology & immunology. “People taking TNF inhibitors didn’t make as many of the potently inhibitory antibodies, and the ones that they did make had largely decayed by five months after the second dose. So even when compared to other immunosuppressed people, people on TNF inhibitors are probably at greater risk for breakthrough infections, especially as immunity wanes and several months have passed since their initial vaccinations. Our data suggests that they should get boosted.”
A previous study co-led by two authors on the current paper — Alfred Kim, MD, PhD, an assistant professor of medicine, and Ali Ellebedy, PhD, an associate professor of pathology & immunology, of medicine and of molecular microbiology — showed that 90% of people taking immunosuppressants (including TNF inhibitors) produce antibodies after COVID-19 vaccination. But that study had looked for the presence or absence of antibodies three weeks after the second vaccine dose. The researchers had not attempted to gauge the quality of the antibody response.
Diamond and first author Rita Chen, an MD/PhD student, launched the new study to investigate the quality of the antibody response to the Pfizer COVID-19 vaccine in immunosuppressed people. In particular, they wanted to know whether vaccination elicits antibodies effective against the delta variant of SARS-CoV-2, the virus that causes COVID-19. Delta currently causes almost all cases of COVID-19 in the U.S.

Phages are viruses that infect bacteria and can also be used to treat human infections. However, as with antibiotics, bacteria can readily evolve resistance to phage attack, highlighting a key limitation to the use of phages as therapeutics. Now, researchers from Yale University have shown that the naturally occurring phage A1-1 kills Shigella flexneri, a major cause of dysentery in sub-Saharan Africa and southern Asia and selects for phage-resistant mutants with reduced virulence. The research is published in Applied and Environmental Microbiology.
That serendipitous finding results from the fact that the phage’s use of a particular surface receptor on the bacterium called OmpA, as a portal to enter and kill S. flexneri, means that bacteria that escape the phage’s attack will either lack OmpA receptors, or that any remaining receptors will have mutated in ways that reduce virulence.
“We sought to discover a phage that was naturally capable of binding to outer membrane proteins of S. flexneri responsible for virulent cell to cell spread of this pathogen in the human intestine, hypothesizing that evolution of phage resistance should alter, or eliminate, this virulence factor protein,” said Kaitlyn E. Kortright, a postdoctoral scientist at Yale.
This, said Kortright, is “a biomedically useful evolutionary tradeoff that improves upon standard phage therapy approaches.”
The researchers pursued phage therapy against S. flexneri because that bacterium was already resistant to conventional antibiotics. Additionally, this pathogen is active primarily in low-income countries, where antibiotics are expensive and often unavailable, and clean drinking water is scarce. Phages, she explained, “might even be useful for treating water sources, by selecting for avirulent S. flexneri.”
The investigators began this project not knowing whether or not a phage existed that can kill S. flexneri. They assumed “that such viruses had naturally evolved, and could be isolated from environmental samples,” said Paul E. Turner, the Rachel Carson Professor of Ecology and Evolutionary Biology at Yale. To increase the odds, “we chose to search in a geographic region renowned for its extreme microbial biodiversity: Cuatro Cienegas, Mexico. Clearly a longshot, but apparently a reasonable idea, because this effort was successful.”
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Materials provided by American Society for Microbiology. Note: Content may be edited for style and length.