Articles from January 2022



How to Reverse Muscle Loss Due to Aging

An international team led by uOttawa Faculty of Medicine researchers have published findings that could contribute to future therapeutics for muscle degeneration due to old age, and diseases such as cancer and muscular dystrophyIn a study appearing in the Journal of Cell Biology, which publishes peer-reviewed research on cellular structure and function, the authors said their work demonstrates the importance of the enzyme GCN5 in maintaining the expression of key structural proteins in skeletal muscle. Those are the muscles attached to bone that breathing, posture and locomotion all rely on.

We found that if you delete GCN5 expression from muscle it will no longer be able to handle extreme physical stress,” says Dr. Keir Menzies, a molecular biologist at the Faculty of Medicine’s Biochemistry, Microbiology and Immunology department and cross-appointed as an associate professor at the Interdisciplinary School of Health Sciences.

Over the span of roughly five years, the uOttawa-led international collaboration painstakingly experimented with a muscle-specific mouse knockout” of GCN5, a well-studied enzyme which regulates multiple cellular processes such as metabolism and inflammation. Through a series of manipulations, scientists produce lab mice in which specific genes are disrupted, or knocked out, to unveil animal models of human disease and better understand how genes work.

In this case, multiple experiments were done to examine the role the GCN5 enzyme plays in muscle fiber. What they found with this line of muscle-specific mouse knockouts was a notable decline in muscle health during physical stress, such as downhill treadmill running, a type of exercise known by athletes to cause micro-tears in muscle fibres to stimulate muscle growth. The lab animals’ muscle fibers became dramatically weaker as they scurried downhill, like those of old mice, while wild-type mice were not similarly impacted

Dr. Menzies, the senior author of the study, says the findings are akin to what is observed in advanced aging, or myopathies and muscular dystrophy, a group of genetic diseases that result in progressive weakness and loss of muscle mass. It was supported by human data, including an observed negative correlation between muscle fiber diameter and Yin Yang 1, a highly multifunctional protein that is pivotal to a slew of cellular processes and found by the Menzies lab to be a target of GCN5. Ultimately, the team’s research found that GCN5 boosts the expression of key structural muscle proteins, notably dystrophin, and a lack of it will reduce them.

Source: https://rupress.org/
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https://www.thebrighterside.news

Rejuvenation by Controlled Reprogramming

On 19 January 2022, co-founders Rick Klausner and Hans Bishop publicly launched an aging research initiative called Altos Labs, with $3 billion in initial investment from backers including tech investor Yuri Milner and Amazon founder Jeff Bezos. This is the latest in a recent surge of investment in ventures seeking to build anti-aging interventions on the back of basic research programs looking at epigenetic reprogramming. In December, cryptocurrency company Coinbase’s cofounder Brian Armstrong and venture capitalist Blake Byers founded NewLimit, an aging-focused biotech backed by an initial $105 million investment, with the University of California, San Francisco’s Alex Marson and Stanford’s Mark Davis as advisors.

The discovery of the Yamanaka factors’ — four transcription factors (Oct3/4, Sox2, c-Myc and Klf4) that can reprogram a differentiated somatic cell into a pluripotent embryonic-like state — earned Kyoto University researcher Shinya Yamanaka a share of the Nobel prize in 2012. The finding, described in 2006, transformed stem cell research by providing a new source of embryonic stem cell (ESC)-like cells, induced pluripotent stem cell (iPSCs), that do not require human embryos for their derivation. But in recent years, Yamanaka factors have also become the focus for another burgeoning area: aging research.

So-called partial reprogramming consists in applying Yamanaka factors to cells for long enough to roll back cellular aging and repair tissues but without returning to pluripotency. Several groups, including those headed by Stanford University’s Vittorio Sebastiano, the Salk Institute’s Juan Carlos Izpisúa Belmonte and Harvard Medical School’s David Sinclair, have shown that partial reprogramming can dramatically reverse age-related phenotypes in the eye, muscle and other tissues in cultured mammalian cells and even rodent models by countering epigenetic changes associated with aging. These results have spurred interest in translating insights from animal models into anti-aging interventions. “This is a pursuit that has now become a race,” says Daniel Ives, CEO and founder of Cambridge, UK-based Shift Bioscience.

The Yamanaka factors that can reprogram cells into their embryonic-like state are at the heart of longevity research

We’re investing in this area [because] it is one of the few interventions we know of that can restore youthful function in a diverse set of cell types,” explains Jacob Kimmel, a principal investigator at Alphabet subsidiary Calico Life Sciences in South San Francisco, California. The zeal is shared by Joan Mannick, head of R&D at Life Biosciences, who says partial reprogramming could be potentially “transformative” when it comes to treating or even preventing age-related diseases. Life Biosciences, a startup co-founded by David Sinclair, is exploring the regenerative capacity of three Yamanaka factors (Oct4, Sox2 and Klf4).

Source: https://www.nature.com/

Eye Scan Predicts Mortality Risk

Using deep learning to predictretinal age” from images of the internal surface of the back of the eye, an international team of scientists has found that the difference between the biological age of an individual’s retina and that person’s real, chronological age, is linked to their risk of death. This ‘retinal age gap’ could be used as a screening tool, the investigators suggest.

Reporting on development of their deep learning model and research results in the British Journal of Ophthalmology, first author Zhuoting Zhu, PhD, at Guangdong Academy of Medical Sciences, together with colleagues at the Centre for Eye Research Australia, Sun Yat-Sen University, and colleagues in China, Australia, and Germany, concluded that in combination with previous research, their study results add weight to the hypothesis that “… the retina plays an important role in the aging process and is sensitive to the cumulative damages of aging which increase the mortality risk.”

Estimates suggest that the global population aged 60 years and over will reach 2.1 billion in 2050, the authors noted.

Aging populations place tremendous pressure on healthcare systems.

But while the risks of illness and death increase with age, these risks vary considerably between different people of the same age, implying that ‘biological aging’ is unique to the individual and may be a better indicator of current and future health. As the authors pointed out, “Chronological age is a major risk factor for frailty, age-related morbidity and mortality. However, there is great variability in health outcomes among individuals with the same chronological age, implying that the rate of aging at an individual level is heterogeneous. Biological age rather than chronological age can better represent health status and the aging process.

Several tissue, cell, chemical, and imaging-based indicators have been developed to pick up biological aging that is out of step with chronological aging. But these techniques are fraught with ethical/privacy issues as well as often being invasive, expensive, and time consuming, the researchers noted.

Source: https://www.genengnews.com/

Injectable Electroactive “Microbots” Heal Broken Bones

Inspired by the growth of bones in the skeleton, researchers at the universities of Linköping in Sweden and Okayama in Japan have developed a combination of materials that can morph into various shapes before hardening. The material is initially soft, but later hardens through a bone development process that uses the same materials found in the skeleton…

When we are born, we have gaps in our skulls that are covered by pieces of soft connective tissue called fontanelles. It is thanks to fontanelles that our skulls can be deformed during birth and pass successfully through the birth canal. Post-birth, the fontanelle tissue gradually changes to hard bone. Now, researchers have combined materials which together resemble this natural process.

We want to use this for applications where materials need to have different properties at different points in time. Firstly, the material is soft and flexible, and it is then locked into place when it hardens. This material could be used in, for example, complicated bone fractures. It could also be used in microrobots – these soft microrobots could be injected into the body through a thin syringe, and then they would unfold and develop their own rigid bones”, says Edwin Jager, associate professor at the Department of Physics, Chemistry and Biology (IFM) at Linköping University.

The idea was hatched during a research visit in Japan when materials scientist Edwin Jager met Hiroshi Kamioka and Emilio Hara, who conduct research into bones. The Japanese researchers had discovered a kind of biomolecule that could stimulate bone growth under a short period of time. Would it be possible to combine this biomolecule with Jager’s materials research, to develop new materials with variable stiffness?

In the study published in Advanced Materials, the researchers constructed a kind of simple “microrobot”, one which can assume different shapes and change stiffness. The researchers began with a gel material called alginate. On one side of the gel, a polymer material is grown. This material is electroactive, and it changes its volume when a low voltage is applied, causing the microrobot to bend in a specified direction. On the other side of the gel, the researchers attached biomolecules that allow the soft gel material to harden. These biomolecules are extracted from the cell membrane of a kind of cell that is important for bone development. When the material is immersed in a cell culture medium – an environment that resembles the body and contains calcium and phosphor – the biomolecules make the gel mineralise and harden like bone.

One potential application of interest to the researchers is bone healing. The idea is that the soft material, powered by the electroactive polymer, will be able to manoeuvre itself into spaces in complicated bone fractures and expand. When the material has then hardened, it can form the foundation for the construction of new bone. In their study, the researchers demonstrate that the material can wrap itself around chicken bones, and the artificial bone that subsequently develops grows together with the chicken bone.

Source: https://liu.se/

How to 3D Print Bandages Using Your Own Skin

If you’re going to go to Mars, you’re probably going to get some cuts and scrapes along the way. Traveling into space is a dangerous endeavor. Humans have evolved to live on the surface of our planet and venturing outside of our atmosphere brings all manner of complications. There are the obvious things, like the lack of food, water, and oxygen. Not to mention the deadly vacuum of space or the potentially toxic environments of other worlds. Then there are less obvious problems, things which might not be immediately deadly but could become a problem in an emergency. Here on Earth, if you become injured you have access to a world’s worth of infrastructure including over the counter medications and healthcare systems. In space, if you get a flesh wound, your crewmates might hear you scream but they’ll have limited ways to help. An experiment by German Space Agency (DLR) is hoping to solve this problem with bioprinted bandages made from an astronaut’s own cells.

SpaceX’s 24th commercial resupply mission to the International Space Station, which launched in late 2021, carried with it a handheld device known as the Bioprint FirstAid Handheld Bioprinter, or Bioprint FirstAid for short.

The device is designed to hold cells from astronauts or Earth-bound patients, infused inside a bio-ink. In the event of an injury, the Bioprint FirstAid would be used to apply a bandage to the injury site in near real-time. The bio-ink mixes with two fast setting gels and will create a covering similar to plaster.

Previously existing technologies for creating similar structures involved bulky machinery and required additional time for the patches to mature. The Bioprint FirstAid has the benefit of being small enough to hold in the hand and it is totally manual, requiring no batteries or other outside power source to use.

For the tests on the ISS, the device won’t have any live cells inside. Instead, it’s carrying fluorescent microparticles which take the place of cells for later observation. The primary objective of these experiments is to test the print capability of the device in microgravity and compare it to performance in Earth gravity.

Taking this technology into space allows researchers to understand the way tissue layers work together in microgravity, which might be fundamentally different to the way they operate here at home.

The findings will not only inform the future of this technology in space but will also provide insight which might be useful on the ground. While the allure of bioprinting technology for space-based missions is immense, this technology will likely do most of its work here on Earth.

Source: https://www.syfy.com/

How to Fix Arthritis in Damaged Knee

By stimulating cells to reproduce, electricity has already been shown to help heal soft tissue injuries. Now, an electricity-producing implantable material likewise appears to boost the regrowth of cartilage in compromised joints. In a study conducted at the University of Connecticut, a team led by Asst. Prof. Thanh Nguyen and postdoctoral fellow Yang Liu explored the use of a “tissue scaffold” made out of nanofibers of a biodegradable polymer known as poly-L lactic acid (PLLA). It had previously been used to accelerate the healing of broken bones.

So-called tissue scaffolds take their name from the fact that they have a scaffolding-like three-dimensional internal structure, which acts as a sort of roosting place for adjacent cells to migrate into and reproduce. Eventually, the scaffolding dissolves and is replaced entirely by the cells, resulting in a solid piece of biological tissue.

Unfortunately, according to the scientists, joint cartilage that has been regrown using conventional scaffolds has tended to be weaker than the original cartilage, causing it to quickly break down under regular use. That’s where the PLLA comes in. Along with being biocompatible, it’s also a piezoelectric material, meaning that it produces a small electrical current when mechanically stressed. Therefore, it was believed that if a tissue scaffold made of the material were to be implanted in an arthritic knee joint, it would continuously produce cartilage-boosting electricity as it was squeezed during activities such as walking. In order to test that theory, pieces of the material were placed in the injured knee joints of rabbits, which regularly hopped on a slowly-moving treadmill. It was found that after one to two months, strong, robust cartilage proceeded to grow back within the joints. By contrast, a control group that received non-piezoelectric tissue scaffolding experienced little healing of the damaged cartilage.

Importantly, the material didn’t contain any chemical growth factors, which may cause unwanted side effects. The researchers now want to test the technology on larger, older animals, and to monitor the regrown cartilage for at least a year or two.

Source: https://today.uconn.edu/

Super-Speedy Diagnosis of Rare Genetic Diseases

About a year ago, Matthew Kunzman’s heart was failing, despite doctors’ best attempts to bolster it with every pump and gadget they could think of. But the 14-year-old has bounced back in large part due to super-speedy genetic sequencing that pinpointed the cause of his disease and helped doctors decide how to treat it — in just 11 and a half hours. That speedy diagnosis — faster than any other medical team has previously reported — resulted from a new approach to DNA sequencing to help patients with deadly and rare diseases. On Wednesday, a team of Stanford researchers and collaborators published a letter in the New England Journal of Medicine reporting that they had sequenced 12 seriously ill patients and successfully diagnosed five of them (including Matthew). In all five cases, the information led to tangible changes in how patients were treated.

Typical turnaround time for diagnosis was around eight hours and as short as seven hours and eighteen minutes – less than half the current record. And the scientists are convinced they can cut that in half yet again. Such speed could be life-saving for critically ill patients, according to Euan Ashley, a Stanford cardiologist and the study’s senior author.

You can not only make care better, and help patients more, but do it cheaper, save money, save the system money,” Ashley said. “It seems like a win, win, win all around.”

There’s a lot to be learned by exploring your genetic code, which influences everything from your height and eye color to your likelihood of developing certain diseases. For doctors, knowing whether a patient’s symptoms are linked to specific DNA mutations — and, if so, which ones — can help them determine what treatments and surgical procedures to try and which ones to avoid. But it typically takes weeks to run, process, and interpret sequencing results. That’s time some patients don’t have. And hospital stays spent chasing down the cause of an unknown disease can cost tens of thousands of dollars.

Ashley wanted to see how quickly he could speed things up. He and his team enrolled a dozen seriously ill patients admitted at Stanford, taking about half a teaspoon of blood from each of them for genetic sequencing. The participants, who ranged in age from 3 months to 57 years old, suffered from everything from seizures to cardiac arrest. Throughout the six-month study, which kicked off in December 2020, researchers tweaked nearly every step of the sequencing process, from having someone run samples from the hospital to the lab to shortening the time needed to prep DNA for sequencing. It was round-the-clock work.

Source: https://www.statnews.com/

Artificial Molecule With Superpowers

When scientists discovered DNA and learned how to control it, not only science but society was revolutionized. Today researchers and the medical industry routinely create artificial DNA structures for many purposes, including diagnosis and treatment of diseases. Now an international research team reports to have created a powerful supermolecule with the potential to further revolutionize science. The work is published in Nature Communications . Authors are from University of Southern Denmark (DK), Kent State University (USA), Copenhagen University (Denmark), Oxford University (UK) and ATDBio (UK). Lead authors are Chenguang Lou, associate professor, University of Southern Denmark and Hanbin Mao, professor, Kent State University, USA.

The researchers describe their supermolecule as a marriage between DNA and peptides

DNA is one of the most important biomolecules, and so are peptides; peptide structures are used, among other things, to create artificial proteins and various nanostructures. If you combine these two, as we have, you get a very powerful molecular tool, that may lead to the next generation of nanotechnology; it may allow us to make more advanced nanostructures, for example, for detecting diseases, says corresponding author Chenguang Lou, associate professor at Department of Physics, Chemistry and Pharmacy, University of Southern Denmark. According to the researchers, another example is that this marriage of peptides to DNA can be used to create artificial proteins, which will be more stable and thus more reliable to work with than natural proteins, which are vulnerable to heat, UV, chemical reagents, etc.

Our next step will be to investigate whether it can be used to explain the cause of Alzheimer’s disease in which malfunctional peptides are culprits, says the other corresponding author, Hanbin Mao, professor at Chemistry and Biochemistry, Kent State University. The research work reports the mechanical properties of a new structure composed of three-stranded DNA structures and three-stranded peptide structures. It may sound simple, but it is far from. It is rare in Nature that DNA and peptide structures are chemically linked like this new structure is. In Nature, they often behave like cats and dogs, though some key interactions are essential to any living organisms. One possible reason for this is their so-called chirality – sometimes also described as handedness.

All biological structures, from molecules to the human body, have a fixed chirality; think of our heart, which is always positioned in the left side of our body. DNA is always right-handed and peptides are always left-handed, so trying to combine them is a highly challenging task. Imagine you want to stack your two hands by matching each finger while both palms face the same direction. You will find out it is impossible to do it. You can only do this if you can trick your two hands into having the same chirality, says Hanbin Mao. This is what the research team has done; tricked the chirality. They have changed the peptide chirality from left to right, so it fits with the chirality of the DNA and works with it instead of repelling it.

This is the first study to show that the chirality of DNA and peptide structures can communicate and interact, when their handedness is changed, says Chenguang Lou. The researchers also report to be the first to provide an answer to why the biological world is chiral: The answer is energy: the chiral world requires the lowest energy to maintain, therefore it is most stable, says Hanbin Mao. In other words: Nature will always seek to spend as little energy as possible.

Source: https://www.sdu.dk/

Successful Transplant of Porcine Heart into Adult Human

In a first-of-its-kind surgery, a 57-year-old patient with terminal heart disease received a successful transplant of a genetically-modified pig heart and is still doing well three days later. It was the only currently available option for the patient. The historic surgery was conducted by University of Maryland School of Medicine (UMSOM) faculty at the University of Maryland Medical Center (UMMC), together known as the University of Maryland Medicine.

This organ transplant demonstrated for the first time that a genetically-modified animal heart can function like a human heart without immediate rejection by the body. The patient, David Bennett, a Maryland resident, is being carefully monitored over the next days and weeks to determine whether the transplant provides lifesaving benefits. He had been deemed ineligible for a conventional heart transplant at UMMC as well as at several other leading transplant centers that reviewed his medical records.

 “It was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice,” said Mr. Bennett, the patient, a day before the surgery was conducted. He had been hospitalized and bedridden for the past few months.  I look forward to getting out of bed after I recover.

The U.S. Food and Drug Administration granted emergency authorization for the surgery on New Year’s Eve through its expanded access (compassionate use) provision. It is used when an experimental medical product, in this case the genetically-modified pig’s heart, is the only option available for a patient faced with a serious or life-threatening medical condition. The authorization to proceed was granted in the hope of saving the patient’s life.

“This was a breakthrough surgery and brings us one step closer to solving the organ shortage crisis. There are simply not enough donor human hearts available to meet the long list of potential recipients,” said Bartley P. Griffith, MD, who surgically transplanted the pig heart into the patient. Dr. Griffith is the Thomas E. and Alice Marie Hales Distinguished Professor in Transplant Surgery at UMSOM. “We are proceeding cautiously, but we are also optimistic that this first-in-the-world surgery will provide an important new option for patients in the future.”

Considered one of the world’s foremost experts on transplanting animal organs, known as xenotransplantation, Muhammad M. Mohiuddin, MD, Professor of Surgery at UMSOM, joined the UMSOM faculty five years ago and established the Cardiac Xenotransplantation Program with Dr. Griffith. Dr. Mohiuddin serves as the program’s Scientific/Program Director and Dr. Griffith as its Clinical Director.

“This is the culmination of years of highly complicated research to hone this technique in animals with survival times that have reached beyond nine months. The FDA used our data and data on the experimental pig to authorize the transplant in an end-stage heart disease patient who had no other treatment options,” said Dr. Mohiuddin.The successful procedure provided valuable information to help the medical community improve this potentially life-saving method in future patients.

Source: https://www.medschool.umaryland.edu/

The Most Powerful Quantum Computer Ever

A team of physicists from the Harvard-MIT Center for Ultracold Atoms and other universities has developed a special type of quantum computer known as a programmable quantum simulator capable of operating with 256 quantum bits, or “qubits.” The system marks a major step toward building large-scale quantum machines that could be used to shed light on a host of complex quantum processes and eventually help bring about real-world breakthroughs in material science, communication technologies, finance, and many other fields, overcoming research hurdles that are beyond the capabilities of even the fastest supercomputers today. Qubits are the fundamental building blocks on which quantum computers run and the source of their massive processing power.

This moves the field into a new domain where no one has ever been to thus far,” said Mikhail Lukin, the George Vasmer Leverett Professor of Physics, co-director of the Harvard Quantum Initiative, and one of the senior authors of the study published today in the journal Nature. “We are entering a completely new part of the quantum world.” 

According to Sepehr Ebadi, a physics student in the Graduate School of Arts and Sciences and the study’s lead author, it is the combination of system’s unprecedented size and programmability that puts it at the cutting edge of the race for a quantum computer, which harnesses the mysterious properties of matter at extremely small scales to greatly advance processing power. Under the right circumstances, the increase in qubits means the system can store and process exponentially more information than the classical bits on which standard computers run

The number of quantum states that are possible with only 256 qubits exceeds the number of atoms in the solar system,” Ebadi said, explaining the system’s vast size.

Already, the simulator has allowed researchers to observe several exotic quantum states of matter that had never before been realized experimentally, and to perform a quantum phase transition study so precise that it serves as the textbook example of how magnetism works at the quantum level.

Source: https://www.thebrighterside.news/