Tag Archives: Aging

Microbiology

Unique combination of intestinal bacteria in Japanese centenarians may be the key to long life

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Reviewed by Megan Craig, M.Sc.May 31 2023

We are pursuing the dream of eternal life. We fast to stay healthy. And each year, we spend billions of kroner on treatment to make sure we stay alive. But some people turn 100 years old all by themselves. Why is that?

Researchers from the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen have set out to find the answer.

Studying 176 healthy Japanese centenarians, the researchers learned that the combination of intestinal bacteria and bacterial viruses of these people is quite unique.

We are always eager to find out why some people live extremely long lives. Previous research has shown that the intestinal bacteria of old Japanese citizens produce brand new molecules that make them resistant to pathogenic – that is, disease-promoting – microorganisms. And if their intestines are better protected against infection, well, then that is probably one of the things that cause them to live longer than others.”

Postdoc Joachim Johansen, first author of the new study

Among other things, the new study shows that specific viruses in the intestines can have a beneficial effect on the intestinal flora and thus on our health.

“Our intestines contain billions of viruses living of and inside bacteria, and they could not care less about human cells; instead, they infect the bacterial cells. And seeing as there are hundreds of different types of bacteria in our intestines, there are also lots of bacterial viruses,” says Associate Professor Simon Rasmussen, last author of the new study.

Joachim Johansen adds that aside from the important, new, protective bacterial viruses, the researchers also found that the intestinal flora of the Japanese centenarians is extremely interesting.

“We found great biological diversity in both bacteria and bacterial viruses in the centenarians. High microbial diversity is usually associated with a healthy gut microbiome. And we expect people with a healthy gut microbiome to be better protected against aging-related diseases,” says Joachim Johansen.

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Once we know what the intestinal flora of centenarians looks like, we can get closer to understanding how we can increase the life expectancy of other people. Using an algorithm designed by the researchers, they managed to map the intestinal bacteria and bacterial viruses of the centenarians.

“We want to understand the dynamics of the intestinal flora. How do the different kinds of bacteria and viruses interact? How can we engineer a microbiome that can help us live healthy, long lives? Are some bacteria better than others? Using the algorithm, we are able to describe the balance between viruses and bacteria,” says Simon Rasmussen.

And if the researchers are able to understand the connection between viruses and bacteria in the Japanese centenarians, they may be able to tell what the optimal balance of viruses and bacteria looks like.

Optimizing intestinal bacteria

More specifically, the new knowledge on intestinal bacteria may help us understand how we should optimize the bacteria found in the human body to protect it against disease.

“We have learned that if a virus pays a bacterium a visit, it may actually strengthen the bacterium. The viruses we found in the healthy Japanese centenarians contained extra genes that could boost the bacteria. We learned that they were able to boost the transformation of specific molecules in the intestines, which might serve to stabilize the intestinal flora and counteract inflammation,” says Joachim Johansen, and Simon Rasmussen adds:

“If you discover bacteria and viruses that have a positive effect on the human intestinal flora, the obvious next step is to find out whether only some or all of us have them. If we are able to get these bacteria and their viruses to move in with the people who do not have them, more people could benefit from them.”

Even though this requires more research, the new insight is significant, because we are able to modify the intestinal flora.

“Intestinal bacteria are a natural part of the human body and of our natural environment. And the crazy thing is that we can actually change the composition of intestinal bacteria. We cannot change the genes – at least not for a long time to come. If we know why viruses and intestinal bacteria are a good match, it will be a lot easier for us to change something that actually affects our health,” says Simon Rasmussen.

Source:

University of Copenhagen – The Faculty of Health and Medical Sciences

Journal reference:

Johansen, J., et al. (2023). Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan. Nature Microbiology. doi.org/10.1038/s41564-023-01370-6.

Microbiology

Tulane receives up to $16 million to move nasal pneumonia vaccine from the lab to clinical trials

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Reviewed by Emily Henderson, B.Sc.Mar 24 2023

The National Institute of Allergy and Infectious Diseases awarded an up to $16 million contract to Tulane University to bring to phase one clinical trial a nasal spray vaccine university researchers invented to thwart antibiotic-resistant Klebsiella pneumoniae, a leading cause of pneumonia.

Antibiotic-resistant bacteria are on the rise and are a significant cause of infections requiring hospitalization among children and the elderly. As doctors try to find new types of antibiotics to fight these so-called superbugs, Tulane University School of Medicine researchers Elizabeth Norton, PhD, and Jay Kolls, MD, inventors of the vaccine, are working to protect people before they are exposed to the pathogens in the first place.

“Multidrug-resistant bacteria are causing more severe infections and are a growing public health threat. Vaccines targeting these pathogens represent the most cost-effective option, particularly if you can use this vaccine to prevent or treat the infection in high-risk individuals,” said Norton, principal investigator and associate professor of microbiology and immunology. “Right now, there is no vaccine on the market that targets this type of pneumonia.”

Klebsiella pneumoniae is the third leading cause of hospital-acquired pneumonia and the second leading cause of bloodstream infections with the highest incidence of serious infections. It is also a major cause of childhood pneumonia in parts of Asia. The Tulane vaccine would target high-risk populations such as immunocompromised individuals, diabetics or organ transplant recipients.

Norton said that while the vaccine targets the Klebsiella bacteria, its unique design gives it the potential to be cross-reactive to other members of the Enterobacteriaceae family, the antibiotic-resistant bacterial species behind many hospital-acquired infections, including E. coli.

The vaccine, called CladeVax, is designed to efficiently target mucosa in the nose, throat and lungs to protect the area most at risk for infection.

The nasal spray vaccine uses an adjuvant -; a compound that stimulates the immune system -; named LTA1 that Norton developed at Tulane. That adjuvant, which is made using a protein derived from the E. coli bacteria, will be combined with a series of proprietary antigens identified by the Kolls lab that include outer membrane proteins from the target bacteria.

This is an entirely novel vaccine platform, from the use of the adjuvant to the needle-less route of administration. This represents an entirely new class of vaccines for bacteria that elicits protection in two ways -; both antibody and T-cell immunity. All current pneumonia vaccines only elicit antibodies against surface carbohydrates. Our platform has the potential advantage of providing a much broader protection against pneumonia.”

Jay Kolls, co-principal investigator, and the John W. Deming Endowed Chair in Internal Medicine

Tulane researchers will first test vaccine formulations in animal models and nonhuman primates for dosing and safety before advancing to clinical trials. The project will include collaborators at Tulane National Primate Research Center, the School of Public Health and Tropical Medicine, Tulane Clinical Translational Unit, and the University of North Carolina as well as contractors for GMP manufacturing.

“If this succeeds, we will have another arsenal for the growing number of antibiotic resistant sources of pneumonia or bloodstream infections,” Norton said. “And we can hopefully expand this nasal spray delivery platform to other infections, working on a single, combination vaccine that is needle-less and targets several organisms at once.”

Source:

Tulane University

Microbiology

Simple blood tests for telomeric protein could provide a valuable screen for certain cancers

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Reviewed by Emily Henderson, B.Sc.Feb 21 2023

Once thought incapable of encoding proteins due to their simple monotonous repetitions of DNA, tiny telomeres at the tips of our chromosomes seem to hold a potent biological function that’s potentially relevant to our understanding of cancer and aging.

Reporting in the Proceedings of the National Academy of Science, UNC School of Medicine researchers Taghreed Al-Turki, PhD, and Jack Griffith, PhD, made the stunning discovery that telomeres contain genetic information to produce two small proteins, one of which they found is elevated in some human cancer cells, as well as cells from patients suffering from telomere-related defects.

Based on our research, we think simple blood tests for these proteins could provide a valuable screen for certain cancers and other human diseases. These tests also could provide a measure of ‘telomere health,’ because we know telomeres shorten with age.”

Jack Griffith, PhD, the Kenan Distinguished Professor of Microbiology and Immunology and Member of the UNC Lineberger Comprehensive Cancer Center

Telomeres contain a unique DNA sequence consisting of endless repeats of TTAGGG bases that somehow inhibit chromosomes from sticking to each other. Two decades ago, the Griffith laboratory showed that the end of a telomere’s DNA loops back on itself to form a tiny circle, thus hiding the end and blocking chromosome-to-chromosome fusions. When cells divide, telomeres shorten, eventually becoming so short that the cell can no longer divide properly, leading to cell death.

Scientist first identified telomeres about 80 years ago, and because of their monotonous sequence, the established dogma in the field held that telomeres could not encode for any proteins, let alone ones with potent biological function.

In 2011 a group in Florida working on an inherited form of ALS reported that the culprit was an RNA molecule containing a six-base repeat which by a novel mechanism could generate a series of toxic proteins consisting of two amino acids repeating one after the other. Al-Turki and Griffith note in their paper a striking similarity of this RNA to the RNA generated from human telomeres, and they hypothesized that the same novel mechanism might be in play.

They conducted experiments – as described in the PNAS paper – to show how telomeric DNA can instruct the cell to produce signaling proteins they termed VR (valine-arginine) and GL (glycine-leucine). Signaling proteins are essentially chemicals that trigger a chain reaction of other proteins inside cells that then lead to a biological function important for health or disease.

Al-Turki and Griffith then chemically synthesized VR and GL to examine their properties using powerful electron and confocal microscopes along with state-of-the-art biological methods, revealing that the VR protein is present in elevated amounts in some human cancer cells, as well as cells from patients suffering from diseases resulting from defective telomeres.

“We think it’s possible that as we age, the amount of VR and GL in our blood will steadily rise, potentially providing a new biomarker for biological age as contrasted to chronological age,” said Al-Turki, a postdoctoral researcher in the Griffith lab. “We think inflammation may also trigger the production of these proteins.”

Griffith noted, “When you go against current thinking, you are usually wrong because you are bucking many people who’ve worked so diligently in their fields. But occasionally scientists have failed to put observations from two very distant fields together and that’s what we did. Discovering that telomeres encode two novel signaling proteins will change our understanding of cancer, aging, and how cells communicate with other cells.

“Many questions remain to be answered, but our biggest priority now is developing a simple blood test for these proteins. This could inform us of our biological age and also provide warnings of issues, such as cancer or inflammation.”

Source:

University of North Carolina Health Care

Journal reference:

Al-Turki, T., et al. (2023) Mammalian Telomeric RNA (TERRA) can be translated to produce valine-arginine and glycine-leucine dipeptide repeat proteins. PNAS. doi.org/10.1073/pnas.2221529120.

Microbiology

Even after decades of research, the cause of the most common form of dementia, Alzheimer’s disease, is unclear. …

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Even after decades of research, the cause of the most common form of dementia, Alzheimer’s disease, is unclear. Evidence that pointed to plaques and tangles of disordered proteins called amyloid beta and tau has been called into question since therapeutics that aim at the protein clumps have not been particularly effective at relieving disease. In recent years, scientists have also found evidence that viral infections may be to blame for some serious long-term diseases; multiple sclerosis, for example, seems to only develop in people who have been infected with Epstein-Barr virus (EBV). The pandemic coronavirus SARS-CoV-2 also appears to have neurological impacts in some people.

Influenza B virus particles, colorized blue, isolated from a patient sample and then propagated in cell culture. Both influenza A and B can cause seasonal flu; however, unlike influenza A virus, which can also infect animals, influenza B only infects humans. Microscopy by John Gallagher and Audray Harris, NIAID Laboratory of Infectious Diseases. Credit: NIAID

Researchers have now used the power of biobanks that contain health data from hundreds of thousands of people to look for links between viral infections like influenza and EBV and neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), generalized dementia, and Parkinson’s disease. Data from FinnGen on over 300,000 people was used to look for associations that were then assessed in the nearly half a million people in the UK Biobank for confirmation. An additional cohort of almost 100,000 people who had not had any neurodegenerative disorder was used as a control group. COVID-19 hospitalizations were not included in this study. The findings have been reported in Neuron.

The research showed that there is a connection between viral infections and neurodegeneration, which is particularly significant for viruses that are able to cross the blood brain barrier and infect the central nervous system, perhaps unsurprisingly. The study authors suggested that these so-called neurotropic viruses may be causing neurodegeneration because of neuroinflammation.

A first pass of the data suggested there were 45 significant associations between viral infections and neurodegenerative disease. After querying the UK Biobank, the researchers refined it to 22 associations.

The top candidate was generalized dementia, which was linked to infections with six different viruses: all influenza, flu and pneumonia, viral pneumonia, viral encephalitis, viral warts, and other viral diseases seem to raise the risk of generalized dementia. The research also showed that anyone who had viral encephalitis was 20 times more likely or more to receive an Alzheimer’s diagnosis compared to people who have not had viral encephalitis.

Severe flu was connected to a greater likelihood of different types of neurodegeneration. Influenza and pneumonia exposures were also linked to an increased risk of all neurodegenerative disorders except multiple sclerosis.

Senior study author Michael Nalls, Ph.D., the NIH Center for Alzheimer’s Related Dementias (CARD) Advanced Analytics Expert Group leader, also noted that the viral infections that are being considered in this study were quite severe and led to hospitalizations; they were not mild cases of the common cold.

“Nevertheless, the fact that commonly used vaccines reduce the risk or severity of many of the viral illnesses observed in this study raises the possibility that the risks of neurodegenerative disorders might also be mitigated,” said Nalls.

“Our results support the idea that viral infections and related inflammation in the nervous system may be common and possibly avoidable risk factors for these types of disorders,” added study co-author Andrew B. Singleton, Ph.D., the director of CARD.

Sources: National Institutes of Health, Neuron


Carmen Leitch

Microbiology

Cancer immunotherapy does not interfere with COVID-19 immunity in vaccinated patients, study shows

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Reviewed by Emily Henderson, B.Sc.Jan 31 2023

Research findings published in Frontiers in Immunology show that cancer immunotherapy does not interfere with COVID-19 immunity in previously vaccinated patients. These findings support recommending vaccination for patients with cancer, including those receiving systemic therapies, say Saint Louis University scientists.

Immunotherapy is a treatment strategy that boosts a patient’s immune system to attack cancerous cells. In this novel study led by Ryan Teague, Ph.D., professor of molecular microbiology and immunology at Saint Louis University’s School of Medicine, the Teague lab studied T cell responses and antibody responses against the SARS-CoV-2 spike protein in vaccinated and unvaccinated patients receiving immunotherapy.

Their research found data to support the clinical safety and efficacy of COVID-19 vaccination in patients receiving immune checkpoint inhibitors, a class of immunotherapy drugs.

It was thought that patients who had recently been vaccinated for or exposed to COVID-19 may have boosted inflammatory responses after immune checkpoint blockade treatment. The study found that immunotherapy did not tend to boost immune responses against COVID-19 in vaccinated patients, supporting the safety of receiving immune checkpoint inhibitors and the vaccine simultaneously.”

Ryan Teague, Ph.D., professor of molecular microbiology and immunology at Saint Louis University’s School of Medicine

Teague notes that several timely factors came together to enable this research. In July 2022, the Teague lab published a study in Cancer Immunology Immunotherapy using a new technique known as Single-Cell RNA Sequencing, which allows researchers to study genetic information at the individual cell level to characterize immune responses after cancer treatment to identify biomarkers that could predict better patient outcomes.

Having collected blood from more than 100 patients with cancer during the COVID-19 pandemic, Teague recognized the opportunity to extend the benefit of this collection toward improving our understanding of patient immune responses against the vaccine.

“The COVID paper came from a unique window of time where we had a pandemic, and we had this valuable collection of patient samples that we could use to ask this timely question,” Teague said.

Additional authors include graduate students Alexander Piening, Emily Ebert, Niloufar Khojandi, and Assistant Professor Elise Alspach, Ph.D., from the Department of Molecular Microbiology and Immunology at SLU’s School of Medicine.

This work was supported by grant number NIH NCI R01 CA238705 from the National Institutes of Health.

Source:

Saint Louis University School of Medicine

Journal reference:

Piening, A., et al. (2022) Immune responses to SARS-CoV-2 in vaccinated patients receiving checkpoint blockade immunotherapy for cancer. Frontiers in Immunology. doi.org/10.3389/fimmu.2022.1022732.

Microbiology

This course teaches students how to connect with older adults to forge intergenerational bonds and help alleviate loneliness and isolation

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Uncommon Courses is an occasional series from The Conversation U.S. highlighting unconventional approaches to teaching.

“Legacy Building with Older Adults – Students Re-Humanizing Health Care”

In March 2020 – as the COVID-19 pandemic was causing widespread lockdowns across the U.S. – I heard from a chaplain friend about older adults who were dying in assisted living facilities and skilled nursing homes indirectly because of social isolation and loneliness.

I was finishing my dissertation, focused on developing a curriculum to assist underrepresented and underserved university students. But after hearing about the needs of older adults, I was moved to do something to help them.

So I shifted my focus and geared my curriculum toward bridging the needs of older adults, who are also often underserved, with young people who are learning the principles of health care.

I developed the concept and then piloted it at my alma mater, the University of Toledo, with counseling and pre-med students. I then further developed it to be suitable for a course aimed at connecting university students in health-care-related fields with older adults who may feel isolated and alone.

This course covers issues in social and cultural determinants of health. Social determinants of health are the conditions in the environments where people live, play, work, attend community events – and where they age. These environments can influence what decisions people make, and the decisions they make can affect a wide range of health and quality-of-life results.

Students in this course connect with older adults once a week, for one hour, in person, via phone or through virtual visits. Throughout the course, students receive training materials in growth mindset, resiliency, mindfulness and goal-setting both for themselves and for the older adults. Students are also trained in reminiscence therapy, which is an approach to help students guide or support the older adult, reaffirming the value of the adults’ stories as they reminisce.

The sessions that involve discussions between students and older adults focus on building rapport and connecting. They also allow for an older adult to impart wisdom and share stories of their past with the students. At the end of the sessions, the older adult participants receive a digital or physical book – which I call a legacy book – that summarizes the stories the older adult shared with the student, to help reinforce that their story matters.

One of the most profound lessons from the pandemic has been that staying connected is important for one’s health.

Emerging research shows how social isolation and loneliness before and during the COVID-19 pandemic are correlated with many physical and mental health problems, including heart disease, diabetes, high blood pressure, heart failure, stroke, dementia, anxiety, depression and suicide.

Researchers estimate that health issues caused by isolation and loneliness increase the risk of early death by 26% and have been equated to smoking 15 cigarettes a day. One of the major ways to build a foundation for addressing isolation and loneliness is building connection between generations.

Many older adults said the most valuable part of the program for them was the relationship and friendship they developed with their legacy builder. One older adult reported back that it was uplifting to know that she could communicate well with the younger generation, and that she is now more confident in talking with her young adult grandchildren.

Older adults can also learn new technology skills from their legacy builder. Many have started texting for the first time and learned how to send pictures via text. Another learned from her legacy builder to create a Facebook account for herself, and she now stays connected with the student through Facebook.

The critical lesson that I hope students take away from the course is that every person has value, and it is worthwhile to listen to the person’s stories to understand what they value and why it matters so much.

I want students to learn how they can reinforce the strengths and self-efficacy in another individual by valuing their stories and lived experiences. I also want health care students in particular to understand that those they serve are the experts of their own lived experiences and have a story worth listening to. On top of that, each person has something to be learned from the other. Ultimately, both leave the conversation feeling edified and uplifted.

The content mainly focuses on communication and listening skills, with mindfulness, growth mindset and goal-setting strategies. Emphasis is placed on gaining skills in interviewing, connection and building rapport.

The course will prepare students to treat the people they serve and care for as human beings, whether or not the student enters the health care field.

We all are children of someone. We all have birthdays. I believe we all deserve to live a life with a sense of dignity, respect and honor. We all need connection, and, whether it be in health care or everyday life, this is a skill that must not be left out of the curriculum.


Jeremy Holloway

The Conversation

Microbiology

Study reveals subtypes and EBV-associated regulatory epigenome reprogramming in nasopharyngeal carcinoma

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Reviewed by Emily Henderson, B.Sc.Dec 16 2022

Researchers from the Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong (HKUMed) discovered a novel subtype of Epstein-Barr Virus (EBV)-positive nasopharyngeal carcinoma (NPC) and EBV-associated immunosuppression in the tumor microenvironment (TME). These findings have provided novel insights into the traditional NPC pathogenesis model and highlights EBV-specific communications in the TME as potential therapeutic target in NPC. The research has been published in eBioMedicine.

Background and research findings

NPC has a high incidence rate in Southeast Asia, in particular Guangdong and Hong Kong. Due to its worldwide rarity, studies on NPC heavily rely on local research teams, and its pathogenesis mechanism remains largely unclear. In Hong Kong, NPC is the commonest cancer type for the men aged 20-44 and ranked 8th highest incidence rate among males. Strikingly, EBV is detected in 95% of the Hong Kong cases. Having thorough understanding of NPC pathogenesis, in particular the role of EBV, is critical for advancing the clinical diagnosis and treatment for this deadly disease and is an active research topic in the field.

The research team used a cutting-edge bioinformatics approach to comprehensively decode the epigenetics of the tumors dissected from NPC patients. EBV+NPC was believed to be massively dysregulated by the global DNA hypermethylation, a phenomenon that denotes a large-scale increase of methyl groups onto the DNA sequences within the cancer cells. These methyl-groups function like an ‘off-switch’ to inactivate tumor-suppressors that safeguard the cells from turning into a tumor, and thereby, promoting tumor development. Moreover, global DNA hypermethylation is rarely observed in non-EBV cancer types proposed to be associated with EBV and is a critical step in NPC pathogenesis.

The research team discovered that, in contrast to what was commonly believed, 20% of NPC cases were characterized by global DNA hypomethylation, which refers to a large-scale decrease of methyl groups onto the DNA sequences in the cancer cells. The study also discovered that EBV may reprogram the cell-cell communications[4]between the cancer cells and the immune cells, and consequently protect the cancer cells from being destroyed by the immune system.

Significance of the study

‘Commonly infected by EBV, the NPC tumours carried distinctive methylation patterns. This finding is not well-recognised by the NPC development model. When global DNA hypomethylation occurs during NPC pathogenesis, whether it occurs as an alternative pathway in a subset of patients and its potential of predicting patients’ survival, clinical features, and response to therapies are critical for understanding NPC and providing personalized treatments for patients.’ commented Dr Dai Wei, Assistant Professor of the Department of Clinical Oncology, School of Clinical Medicine, HKUMed.

Professor Maria Li Lung, Emeritus Professor of the Department of Clinical Oncology, School of Clinical Medicine, HKUMed, added, ‘Since the immunosuppressive cell-cell communications were associated with EBV, these communications are highly-specific to the tumours and could be potential therapeutic targets and biomarkers in NPC.’ ‘We are now designing experiments to explore this feasibility and understand the clinical impacts of NPC subtypes. We hope the work can be beneficial to NPC patients in Hong Kong.’

About the research team

This research was co-supervised by Dr Dai Wei, Assistant Professor, and Professor Maria Li Lung, Emeritus Professor of the Department of Clinical Oncology, School of Clinical Medicine, HKUMed. Dr Larry Chow Ka-yue and Mr Dittman Chung Lai-shun from the Department of Clinical Oncology, School of Clinical Medicine, HKUMed, are the co-first authors, Dr Tao Lihua, Scientific Officer, provided support to the research.

The collaborators included Dr Chan Kui-fat and Dr Stewart Tung Yuk from Department of Clinical Oncology and Department of Clinical Pathology from the Tuen Mun Hospital, Hong Kong; Professor Roger Ngan Kai-cheong, Professor Ng Wai-tong, Professor Anne Lee Wing-mui, Professor Dora Kwong Lai-wan, Dr Victor Lee Ho-fun and Dr Lam Ka-on from the Department of the Clinical Oncology, School of Clinical Medicine, HKUMed; Dr Yau Chun-chung from Department of Oncology from Princess Margaret Hospital, Hong Kong; Professor Chen Honglin and Dr Liu Jiayan from Department of Microbiology, School of Biomedical Sciences, HKUMed.

Source:

The University of Hong Kong

Journal reference:

Chow, L. K-Y., et al. (2022) Epigenomic landscape study reveals molecular subtypes and EBV-associated regulatory epigenome reprogramming in nasopharyngeal carcinoma. eBioMedicine. doi.org/10.1016/j.ebiom.2022.104357.

Microbiology

Shocking Study Finds Severe COVID-19 Linked With Molecular Signatures of Brain Aging

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Scientists emphasize the value of neurological follow-up in recovered individuals.

It’s true that COVID-19 is primarily a respiratory disease. However, neurological symptoms have been described in many COVID-19 patients, including in recovered individuals. In fact, a range of symptoms has been reported by patients including brain fog or lack of focused thinking, memory loss, and depression. Additionally, scientists have demonstrated that patients with severe COVID-19 exhibit a drop in cognitive performance that mimics accelerated aging. But, what has been lacking is molecular evidence for COVID-19’s aging effects on the brain.

In a series of experiments, scientists discovered that gene usage in the brains of patients with COVID-19 is similar to those observed in aging brains. The scientists, from Beth Israel Deaconess Medical Center (BIDMC), used a molecular profiling technique called RNA sequencing to measure the levels of every gene expressed in a particular tissue sample. This allowed them to assess changes in gene expression profiles in the brains of COVID-19 patients and compare them to those changes observed in the brains of uninfected individuals. The team’s analysis suggested that many biological pathways that change with natural aging in the brain also changed in patients with severe COVID-19. The study was published on December 5 in the journal Nature Aging.

“Ours is the first study to show that COVID-19 is associated with the molecular signatures of brain aging,” said co-first and co-corresponding author Maria Mavrikaki, PhD, an instructor of pathology at BIDMC and Harvard Medical School. “We found striking similarities between the brains of patients with COVID-19 and aged individuals.”

Mavrikaki and colleagues analyzed a total of 54 postmortem human frontal cortex tissue samples from adults 22 to 85 years old. Of these, 21 samples were from severe COVID-19 patients and one from an asymptomatic COVID-19 patient who died. These samples were age- and sex-matched to uninfected controls with no history of neurological or psychiatric disease. The scientists also included an age-and sex- matched uninfected Alzheimer’s disease case for analysis as a control to a COVID-19 case which had co-morbid Alzheimer’s disease, as well as an additional independent control group of uninfected individuals with a history of intensive care or ventilator treatment.

“We observed that gene expression in the brain tissue of patients who died of COVID-19 closely resembled that of uninfected individuals 71 years old or older,” said co-first author Jonathan Lee, PhD, a postdoctoral research fellow at BIDMC and Harvard Medical School. “Genes that were upregulated in aging were upregulated in the context of severe COVID-19; likewise, genes downregulated in aging were also downregulated in severe COVID-19. While we did not find evidence that the SARS-CoV-2 virus was present in the brain tissue at the time of death, we discovered inflammatory patterns associated with COVID-19. This suggests that this inflammation may contribute to the aging-like effects observed in the brains of patients with COVID-19 and long COVID.”

“Given these findings, we advocate for neurological follow-up of recovered COVID-19 patients,” said senior and co-corresponding author Frank Slack, PhD, director of the Institute for RNA Medicine at BIDMC and the Shields Warren Mallinckrodt Professor of Medical Research at Harvard Medical School. “We also emphasize the potential clinical value in modifying the factors associated with the risk of dementia — such as controlling weight and reducing excessive alcohol consumption — to reduce the risk or delay the development of aging-related neurological pathologies and cognitive decline.”

Better understanding of the molecular mechanisms underlying brain aging and cognitive decline in COVID-19 could lead to the development of novel therapeutics to address cognitive decline observed in COVID-19 patients. The team is now trying to understand what drives the aging-like effects in the brains of COVID-19 patients. 

Reference: “Severe COVID-19 is associated with molecular signatures of aging in the human brain” by Maria Mavrikaki, Jonathan D. Lee, Isaac H. Solomon and Frank J. Slack, 5 December 2022, Nature Aging.
DOI: 10.1038/s43587-022-00321-w

Isaac H. Solomon, MD, PhD, of Brigham and Women’s Hospital, also contributed to this work, which was supported by the National Institute of Aging (NIA; R01 AG058816). The authors declare no conflicts of interest.

Beth Israel Deaconess Medical Center

Microbiology

Stanford Researchers Find COVID-19 Pandemic Stress Physically Aged Teens’ Brains

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The brains of adolescents who were assessed after the COVID pandemic shutdowns ended appeared several years older than those of teens who were assessed before the pandemic. Until now, such accelerated changes in “brain age” have only been seen in children experiencing chronic adversity, such as neglect and family dysfunction.

Pandemic-related stressors have physically altered adolescents’ brains, making their brain structures appear several years older than the brains of comparable peers before the pandemic. This is according to a new study from Stanford University that was published on December 1, 2022, in the journal Biological Psychiatry: Global Open Science.

In 2020 alone, reports of anxiety and depression in adults rose by more than 25 percent compared to previous years. The new findings indicate that the neurological and mental health effects of the COVID-19 pandemic on adolescents may have been even worse.

“We already know from global research that the pandemic has adversely affected mental health in youth, but we didn’t know what, if anything, it was doing physically to their brains,” said Ian Gotlib, the Marjorie Mhoon Fair Professor of Psychology in the School of Humanities & Sciences, who is the first author on the paper.

Gotlib notes that as we age, changes in brain structure occur naturally. During puberty and early teenage years, kids’ bodies experience increased growth in both the hippocampus and the amygdala, areas of the brain that respectively control access to certain memories and help to modulate emotions. At the same time, tissues in the cortex, an area involved in executive functioning, become thinner.

By comparing MRI brain scans from a cohort of 163 children taken before and during the pandemic, Gotlib’s study showed that this developmental process sped up in adolescents as they experienced the COVID-19 lockdowns. Until now, he says, these sorts of accelerated changes in “brain age” have appeared only in children who have experienced chronic adversity, whether from violence, neglect, family dysfunction, or a combination of multiple factors.

Although those experiences are linked to poor mental health outcomes later in life, it’s unclear whether the changes in brain structure that the Stanford team observed are linked to changes in mental health, Gotlib noted.

“It’s also not clear if the changes are permanent,” said Gotlib, who is also the director of the Stanford Neurodevelopment, Affect, and Psychopathology (SNAP) Laboratory at Stanford University. “Will their chronological age eventually catch up to their ‘brain age’? If their brain remains permanently older than their chronological age, it’s unclear what the outcomes will be in the future. For a 70- or 80-year-old, you’d expect some cognitive and memory problems based on changes in the brain, but what does it mean for a 16-year-old if their brains are aging prematurely?”

Originally, Gotlib explained, his study was not designed to look at the impact of COVID-19 on brain structure. Before the pandemic, his lab had recruited a cohort of children and adolescents from around the San Francisco Bay Area to participate in a long-term study on depression during puberty – but when the pandemic hit, he could not conduct regularly-scheduled MRI scans on those youth.

“Then, nine months later, we had a hard restart,” Gotlib said.

Once Gotlib could continue brain scans from his cohort, the study was a year behind schedule. Under normal circumstances, it would be possible to statistically correct for the delay while analyzing the study’s data – but the pandemic was far from a normal event. “That technique only works if you assume the brains of 16-year-olds today are the same as the brains of 16-year-olds before the pandemic with respect to cortical thickness and hippocampal and amygdala volume,” Gotlib said. “After looking at our data, we realized that they’re not. Compared to adolescents assessed before the pandemic, adolescents assessed after the pandemic shutdowns not only had more severe internalizing mental health problems, but also had reduced cortical thickness, larger hippocampal and amygdala volume, and more advanced brain age.”

These findings could have major implications for other longitudinal studies that have spanned the COVID pandemic. If kids who experienced the pandemic show accelerated development in their brains, scientists will have to account for that abnormal rate of growth in any future research involving this generation.

“The pandemic is a global phenomenon – there’s no one who hasn’t experienced it,” said Gotlib. “There’s no real control group.”

These findings might also have serious consequences for an entire generation of adolescents later in life, added co-author Jonas Miller. During the study, he was a postdoctoral fellow in Gotlib’s lab, and he is now an assistant professor of psychological sciences at the University of Connecticut.

“Adolescence is already a period of rapid reorganization in the brain, and it’s already linked to increased rates of mental health problems, depression, and risk-taking behavior,” Miller said. “Now you have this global event that’s happening, where everyone is experiencing some kind of adversity in the form of disruption to their daily routines – so it might be the case that the brains of kids who are 16 or 17 today are not comparable to those of their counterparts just a few years ago.”

In the future, Gotlib plans to continue following the same cohort of kids through later adolescence and young adulthood, tracking whether the COVID pandemic has changed the trajectory of their brain development over the long term. He also plans to track the mental health of these teens and will compare the brain structure of those who were infected with the virus with those who weren’t, with the goal of identifying any subtle differences that may have occurred.

Reference: “Effects of the COVID-19 Pandemic on Mental Health and Brain Maturation in Adolescents: Implications for Analyzing Longitudinal Data” by Ian H. Gotlib, Jonas G. Miller, Lauren R. Borchers, Sache M. Coury, Lauren A. Costello, Jordan M. Garcia and Tiffany C. Ho, 1 December 2022, Biological Psychiatry: Global Open Science.
DOI: 10.1016/j.bpsgos.2022.11.002

The study was supported by funding from the National Institutes of Health (R37MH101495 to Ian Gotlib).

Gotlib is also a member of Bio-X, the Maternal & Child Health Research Institute, the Precision Health and Integrated Diagnostics Center, and the Wu Tsai Neurosciences Institute. He is also a faculty affiliate of the Stanford Center on Longevity.

Stanford University

Microbiology

One of the most significant consequences of climate change is the greenhouse gases generated from the microbial decomposition …

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One of the most significant consequences of climate change is the greenhouse gases generated from the microbial decomposition of organic matter in thawing permafrost soil. Permafrost refers to ground soil frozen at 0℃ or lower, year after year. Permafrost regions of the Earth are mostly found in the north and south poles. During summer, some thawing of the permafrost landscape is considered normal, but with climate change, thawing has increased annually.

Studies of permafrost soil have previously identified ancient bacteria, viruses, fungi, and even protozoans that can potentially become infectious after several years of being frozen. Apart from identification, the global impact of the microbial composition of permafrost on human health remains largely undetermined. 

More recently, DNA was isolated from soil samples in the carbon-rich Yedoma permafrost of Siberia. The Yedoma permafrost is known to have preserved animal remains like mammoths and ancient microbial content. An international team of scientists from Russia and Germany conducted a ‘metagenomic’ analysis of various soil samples from the Yedoma permafrost, which involves the detailed characterization of all DNA extracted from multiple soil samples. Their studies from the Yedoma soils have identified bacterial genes from several bacterial species with no specific correlation to the age of the permafrost. Interestingly, a high frequency of the beta-lactamase gene was detected within the identified bacterial genomes. What does this mean? The DNA samples belong to diverse bacterial species, and all carry the gene for the enzyme beta-lactamase. Beta-lactamases are enzymes that cause the inactivation of penicillin-derived antibiotics, thereby conferring antibiotic resistance to the bacteria carrying them (in their genome or plasmids). 

Active microbial life has been discovered in the arctic before. But the discovery of bacterial DNA, a large proportion of which carries antibiotic resistance, is unexpected. This finding is even more perplexing to scientists because these soils have remained far removed from human civilization that have heavy antibiotic usage. The acquisition of antibiotic resistance is technically possible outside a clinical setting. Bacteria acquire genes from their environment all the time. However, the potential danger of thawing permafrost and the release of bacterial DNA offering antibiotic resistance is concerning.

Antimicrobial resistance (AMR) is a global health issue that severely challenges our ability to treat bacterial infections effectively. Tracking and early identification of AMR in clinical settings is key to reducing its spread. The discovery of antibiotic resistance in permafrost does not directly affect clinical care today but has implications for the future of AMR, especially with a rising concern about climate change. 


Anusha Naganathan