Discovered in the 1970s, circadian clocks are essential for the regulation of biological time in most cells in the human body. These internal mechanisms adjust biological processes to a 24-hour cycle, allowing the synchronisation of cellular functions with daily variations in the environment. Circadian rhythms, which are coordinated by a central clock in the brain that communicates with clocks in different peripheral tissues, influence many functions, from our sleep patterns to our ability to metabolise food.
A team led by Dr. Salvador Aznar Benitah, an ICREA researcher at IRB Barcelona, and Dr. Pura Muñoz-Cánoves, an ICREA researcher in the Department of Medicine and Life Sciences at the Pompeu Fabra University (UPF), has described how the synchronisation between the central clock and peripheral clocks in muscle and skin plays a key role in ensuring the correct function of these tissues, as well as preventing degenerative processes associated with ageing.
The results of this work have been published in two articles in high-impact journals. In this regard, the research on the synchronisation between the central and peripheral clocks appears in Science, while the work on the coordination between the central clock and skin peripheral clock has been released in Cell Stem Cell. Both studies reveal the common mechanisms that underscore the importance of this coordination to uphold the optimal functionality of muscle and skin.
The work also describes the remarkable degree of autonomy of the peripheral clocks, which can maintain 24-h cycles and manage approximately 15% of circadian functions in the absence of the central clock.
“It is fascinating to see how synchronisation between the brain and peripheral circadian clocks plays a critical role in skin and muscle health, while peripheral clocks alone are autonomous in carrying out the most basic tissue functions,” says Dr. Aznar Benitah, head of the Stem Cell and Cancer laboratory at IRB Barcelona.
“Our study reveals that minimal interaction between only two tissue clocks (one central and the other peripheral) is needed to maintain optimal functioning of tissues like muscles and skin and to avoid their deterioration and ageing. Now, the next step is to identify the signalling factors involved in this interaction, with potential therapeutic applications in mind,” explains Dr. Muñoz-Cánoves, a UPF Professor who is now a Principal Investigator at Altos Labs (San Diego, US).
Coordination with the muscle peripheral clock maintains muscle function and prevents premature ageing
The study published in Science on the communication between the brain and muscle confirmed that the coordination between the central and peripheral clocks is crucial for maintaining daily muscle function and preventing the premature ageing of this tissue. Restoration of the circadian rhythm reduces the loss of muscle mass and strength, thereby improving deteriorated motor functions in experimental mouse models.

The results of the study have also demonstrated that time-restricted feeding (TRF), which involves eating only in the active phase of the day, can partially replace the central clock and enhance the autonomy of the muscle clock. More relevant still is that this restoration of the circadian rhythm through TRF can mitigate muscle loss, the deterioration of metabolic and motor functions, and the loss of muscle strength in aged mice.
These findings have significant implications for the development of therapies for muscular ageing and the enhancement of physical performance in older age. Drs. Arun Kumar and Mireia Vaca Dempere, both from the UPF, are the first authors of this study, which has also received contributions from Drs. Eusebio Perdiguero and Antonio Serrano, previously at the UPF and now at Altos Labs.
The peripheral clock of the skin integrates and modulates brain signals
In the study published in Cell Stem Cell, the team has demonstrated that the skin circadian clock is pivotal in coordinating the daily physiology of this tissue. By integrating brain signals, and sometimes by modifying them, this coordination ensures the correct functioning of the skin.
A surprising discovery was that, in the absence of the peripheral clock, the central body clock maintains the circadian rhythm of the skin but it works in the opposite way as usual (that is to say, on an opposite schedule). For example, the researchers observed that DNA replication, if regulated only by the central clock, would occur during the daytime, when skin is exposed to ultraviolet light, which would increase the risk of accumulating mutations. This phenomenon highlights the importance of the peripheral clock, which not only receives signals from the central clock — which coordinates the rhythms of the entire organism — but also adapts these signals to the specific needs of the tissue in which they are (in the case of skin stem cells, DNA replication peaks after exposure to ultraviolet light during the day).
Dr. Thomas Mortimer, a postdoctoral fellow at IRB Barcelona, and Dr. Patrick-Simon Welz, from the Hospital del Mar Research Institute, have headed this project, together with Drs. Aznar Benitah and Muñoz-Cánoves.
The results of the two studies stem from international collaboration with researchers from the University of California and the University of Texas Health in San Antonio (both in the US), the University of Lübeck in Alemania, the Karolinska Institute in Sweden, the Humanitas University in Italy, and Altos Labs San Diego Institute of Science in the US. The project was supported by funding from the European Research Council, the EU H2020 programme, the Ministry of Science, Innovation and Universities, the Government of Catalonia, the Lilliane Bettencourt Foundation, “la Caixa” Foundation, the Marató de TV3 Foundation, the BBVA Foundation and the Novo Nordisk Foundation.

Vigorous exercise burns fat more in males than in females — an unexpected finding from the largest study to date to explore how exercise affects the body.
“Everyone knows that exercise is good for you, but no one knows exactly why,” said Joshua Adkins, a scientist at the Department of Energy’s Pacific Northwest National Laboratory and a corresponding author of a study published online May 1 in Nature Metabolism. “We don’t know what’s happening in the body that creates such great benefits.”
The results come from the Molecular Transducers of Physical Activity Consortium (MoTrPAC), a years-long study investigating the molecular actions that translate vigorous movement into a glut of health benefits. The collaboration stretches across more than two dozen sites around the country, involving more than 100 scientists.
The group published its core paper in the journal Nature on May 1, finding that the effects of exercise are extensive, affecting more than 35,000 molecules. No tissue studied goes unchanged.
The study subjects were rats, which share much of their basic physiology with people. This group of scientists is now studying more than 1,500 people, using the findings from rats as a starting point to investigate what happens in humans.
Overall, the MoTrPAC team looked at 18 tissue types as well as blood. They found molecular signals in both males and females that demonstrated extensive benefits of exercise: enhanced liver function, stronger heart muscle, enriched immunity, and reduced inflammation in the lungs and gut. Throughout the body, cellular organelles known as mitochondria — the energy producers in cells — become healthier after exercise.
The most remarkable difference between the sexes was in the fat tissue, the subject of the Nature Metabolism paper.

“We found that fat tissue between males and females is very different even in sedentary animals,” said Christopher Newgard, a corresponding author and director of the Duke Molecular Physiology Institute. “But then I was truly gobsmacked with how amazingly different the sex-dependent responses to exercise are. Males burn fat for energy while females preserve their fat mass. This is brought about by many differences in molecular responses lurking beneath the surface in fat from male compared to female rats. The dichotomy is truly striking.”
In addition to Adkins and Newgard, corresponding authors of the Nature Metabolism paper are Sue Bodine of the Oklahoma Medical Research Foundation and Simon Schenk of the University of California San Diego. The paper has three “first authors” from PNNL: Gina Many, James Sanford and Tyler Sagendorf.
Findings from rats on the run
The results are based on an analysis of tissues and blood samples from rats that ran on treadmills in a research laboratory at the University of Iowa. The team made thousands of measurements of proteins, molecular messengers known as transcripts, and chemical compounds called metabolites. Those measurements give scientists clues about what’s actually happening in the body. Behind every breath, thought, movement or step on a treadmill, there’s a cascade of molecular actions that make things happen and affect the body.
The samples were sent to several laboratories for analysis. Scientists at PNNL analyzed the proteins in the fat samples — a challenging task because fat has few proteins relative to lipids. The team looked at white adipose tissue, by far the most prevalent form of fat in the body.
Scientists studied rats that ran five days a week for one, two, four or eight weeks, comparing them to sedentary rats. The team studied healthy, lean animals. The scientists note that the study’s finding can’t be automatically applied to animals that are obese, for instance, or to other types of exercises, such as strength training.

Less fat, same amount of fat, healthier fat
The difference in fat characteristics was remarkable even between male and female rats that were sedentary. More than 20,000 molecular measures were different. Overall, the fat in female rats was healthier both before and after training.
Male and female sedentary rats did have one characteristic in common: They all gained weight throughout the study.
The differences in rats that ran the treadmill were even more noteworthy. Males burned fat and kept it off. Females initially burned fat, but by the end of eight weeks, their fat stores were back to where they were when they started. Male rats that exercised lost fat. Female rats that exercised did not lose fat — but they did not gain fat as their sedentary counterparts did.
Exercise did make the fat stores of both sexes healthier — more metabolically active and energetic, with fewer signals like those involved in obesity. This was more noteworthy in the male rats, whose fat was less healthy to start.
“We saw both sexes mobilize their metabolism to get the energy they need,” said first author Gina Many. “But they get their energy in different ways. Females do so without drawing much from their fat stores, likely because those are critical to reproductive health.”
In recent decades, scientists have learned that fat isn’t simply a blob of unwelcome weight. It’s a major organ that runs throughout our body, like the skin, that secretes hormones and other compounds that play an important role in our health. Fat is a font of both health and disease.
A road map from rats to people
“These findings help set the landscape to understand disease risk and establish a basis for more personalized and targeted health interventions,” said Many.
The investigators said the results make it crucial that health studies include women and men, noting that when it comes to exercise, many more men than women have been studied.
“This study really opened my eyes,” said Newgard. “The differences between the sexes are much more vast than I would have anticipated. This is changing the way I am approaching other studies, including one on insulin resistance in males and females. These findings provide a road map for those experiments.”
The MoTrPAC study is funded by the National Institutes of Health Common Fund. Many of the protein analyses discussed in the Nature Metabolism paper were done at the Environmental Molecular Sciences Laboratory, a DOE Office of Science user facility on the PNNL campus. The technologies used by the PNNL team in the MoTrPAC experiment are also used to explore molecular reactions important to climate, energy and the environment.

Hvidovre Hospital has the world’s first prototype of a sensor capable of detecting errors in MRI scans using laser light and gas. The new sensor, developed by a young researcher at the University of Copenhagen and Hvidovre Hospital, can thereby do what is impossible for current electrical sensors — and hopefully pave the way for MRI scans that are better, cheaper and faster.
MRI scanners are used by doctors and healthcare professionals every day to get a unique look into the human body. In particular, they are used to study the brain, vital organs and other soft tissues by way of 3D images of exceptional quality compared to other types of medical imaging.
While this makes the advanced tool invaluable and nearly indispensable for healthcare professionals, there is still room for improvement.
The strong magnetic fields inside MRI scanners have fluctuations that create errors and disturbances in scans. Consequently, these expensive machines (hundreds of Euros per hour) must be calibrated regularly to reduce errors.
There are also special scanning methods, which unfortunately cannot be done in practice today. Among them, so-called spiral sequences that could reduce scanning time, e.g., when diagnosing blood clots, sclerosis and tumors. Spiral sequences would also be an attractive tool in MRI research, where, among other things, they could provide researchers and health professionals with new knowledge about brain diseases. But due to the highly unstable magnetic field, performing these types of scans is not currently an option.
In theory, the problem can be solved with a sensor that reads and maps changes in the magnetic field. Thereafter, it is relatively simple to correct the errors in images with a computer. In practice, this has been difficult with the current technology, as otherwise suitable sensors interfere with the magnetic field because they are electric and connected to metal cables.
A new invention hopes to make this problem a thing of the past. To combat the problem, a researcher from the Niels Bohr Institute and The Danish Research Centre for Magnetic Resonance (DRCMR) has developed a sensor that uses laser light in fiber cables and a small glass container filled with gas. The prototype is ready and works.

“First we demonstrated that it was theoretically possible, and now we have proven that it can be done in practice. In fact, we now have a prototype that can basically make the measurements needed without disturbing the MRI scanner. It needs to be developed more and fine-tuned, but has the potential to make MRI scans cheaper, better and faster — although not necessarily all three at once,” laughs Hans Stærkind, a postdoc at the Niels Bohr Institute and DRCMR at Hvidovre Hospital. Stærkind is the main architect behind the sensor and device that comes with it.
“An MRI scanner can already produce incredible images if one takes their time. But with the help of my sensor, it is imaginable to use the same amount of time to produce even better imagery — or spend less time and still get the same quality as today. A third scenario could be to build a cheaper scanner that, despite a few errors, could still deliver decent image quality with the help of my sensor,” says the researcher.
How the prototype works
MRI scanners use powerful magnets to produce a strong magnetic field that forces protons in the body’s water, carbohydrates and proteins to align themselves with the magnetic field. When radio waves are pulsed through a patient, the protons are stimulated and temporarily spin out of that equilibrium. When they subsequently return to alignment with the magnetic field, they release radio waves that can be used to form real-time 3D images of whatever is being scanned.
Hans Stærkind’s prototype works using a device for sending and receiving laser light that looks like a 1990’s stereo system. It sends laser light through fiber optic cables — i.e., without any metal — and into four sensors located in the scanner.
Within the sensors, the light passes through a small glass container containing a caesium gas, which absorbs the light at the right light frequencies.

“When the laser has just the right frequency while passing through the gas, there is a resonance between the waves of light and electrons in the caesium atoms. But the frequency — or wavelength — at which this happens changes when the gas is exposed to a magnetic field. In this way, we can measure the strength of the magnetic field by finding out what the right frequency is. This happens completely automatically and lightning fast by the receiving device,” explains the researcher.
As disturbances in an MRI scanner’s ultra-powerful magnetic field occur, Hans Stærkind’s prototype maps where in the magnetic field they are occurring and by what strength the field has changed. In the near future, this could mean that disturbed and faulty images could be corrected — based on the data collected by the sensors, and subsequently made accurate and entirely usable.
Innovation with commercial prospects — when data is in place
The prototype is currently housed at DRCMR at Hvidovre Hospital in Copenhagen, which is also where the idea was conceived.
“The original idea came from my supervisor here at DRCMR, Esben Petersen, who is unfortunately no longer with us. He saw huge potential in developing a sensor based on lasers and gas that would be able to measure the magnetic fields without disturbing them,” says Hans Stærkind.
With the help of quantum physicists at the Niels Bohr Institute, including Professor Eugene Polzik, Stærkind developed the idea into an actual theory. And with the prototype, he has now put that theory into practice.
“The prototype is designed in such a way that it is already suitable in hospital contexts as a robust and well-functioning instrument. And so far, our tests have shown that it works as it should. One can imagine that this invention will eventually be integrated directly into new MRI scanners,” says Stærkind.
For now, the prototype will be developed further so that its measurements become even more accurate.
“We need to collect data and fine-tune it so that it continuously becomes a better and better tool for finding errors in scans. After that, we’ll move on to the exciting work of correcting errors in MRI images, and find out in what situations and which types of scans our sensor can make a significant difference,” says the researcher.
According to Stærkind, the immediate target group for his sensor are MRI research units. But he also hopes that one of the large MRI manufacturers finds out about the new technology, in the slightly longer term.
“Once the prototype has been refined in a 2.0 version and its qualities documented with plenty of data from actual scans here at the hospital, we will see where this goes. It certainly has the potential to improve MRI scans in a unique way that can benefit doctors and, not least, patients,” says the researcher.
Facts about MRI scanners
Despite having been around since 1977, MRI scanners remain one of the most advanced medical technologies. In fact, everything from quantum mechanics, superconducting magnets and advanced mathematics and computer science is a prerequisite for them to work.
The devices consist of a giant magnet with a magnetic force so great, that it must be cooled to -269° C or risk going up in smoke — literally. Among other things, this is done with liquid helium and makes the machine’s primary magnet superconductive.
That is, the electricity that drives electromagnetism has no resistance, and constantly runs in a closed circuit without the supply of electricity. The whopping electric bills associated with operating MRI’s are primarily due to their cooling.
Within an MRI scanner, there are a number of other electromagnets that can be used to control the magnetic field, so that you can look into specific parts of the body and do so from different angles.
The very high strength of the magnetic fields requires that belt buckles, coins and all other metal objects be kept safely away from the machine in another room. In fact, a number of accidents with MRI scanners have occurred due to their exceptionally powerful magnetism. For example, a wheelchair could be hurled towards the scanner regardless of who or what was standing in its way. But if all of the necessary safety precautions are followed, there are no known risks from an MRI scan itself.
The scanner’s strong magnetic field forces protons in the body’s water molecules — which are themselves magnets, called spins — to align themselves with the magnetic field. Radio waves are then sent through the patient, which temporarily spin the protons out of that equilibrium. When realigned, the energy is released again in measurable radio waves.
With the help of a computer, magnetic resonance imaging (MRI) can be used to create millimetre-precise 3D images of a patient’s soft tissue from any angle.
Facts: How it works
Four sensors are distributed in the MRI scanner. One remains out of range of the magnetic field and acts as a control.
Laser light inside the sensors with certain light frequencies passes through a small glass container with cesium gas.
The frequency of the laser creates resonance in the electrons of the cesium atoms. This dims the light to a degree that can be detected.
If the gas is exposed to a magnetic field, the triggering frequency changes depending on the strength of the magnetic field.
Fluctuations in the magnetic field of the MRI scanner can thus be registered and data can subsequently reveal errors in the MRI scan.
Facts: Resonance
In the Adventures of Tintin, opera diva Bianca Castafiore shatters a crystal glass by hitting the glass’s resonant frequency with the power of her voice. Everything has a certain frequency that it likes to vibrate — or oscillate at.
If as a child, or adult, you ever set a swing in motion by pumping it back and forth, you used the resonance frequency to do so. When something resonates, its oscillations are amplified.
If you send light into a gas, it will pass straight through — unless it has just the right frequency. At a certain frequency, light is absorbed because it oscillates at the same frequency as the electrons in the gas atoms.
The electrons oscillate more and more while absorbing the energy, and the light is then re-emitted in all directions as the electrons fall back into place.
If you look at it, you will see that the ray dims and the gas vapor lights up.
Resonance, therefore, is when you hit the natural frequency of a system so that it oscillates. This frequency is called resonance frequency.

LMU researchers have deciphered the complex interplay of various enzymes around the innate immune receptor toll-like receptor 7 (TLR7), which plays an important role in defending our bodies against viruses.
Toll-like receptor 7 (TLR7), located in the dendritic cells of our immune system, plays a crucial role in our natural defense against viruses. TLR7 recognizes single-stranded viral and other foreign RNA and activates the release of inflammatory mediators. Dysfunctions of this receptor also play a key role in autoimmune diseases, making it all the more important to understand, and ideally modulate, the exact activation mechanism of TLR7.
Researchers led by Professor Veit Hornung and Marleen Bérouti from the Gene Center Munich and the Department of Biochemistry at LMU have now managed to gain deeper insights into the complex activation mechanism. It was known from earlier studies that complex RNA molecules have to be cut up first so that the receptor is able to recognize them. Using a wide range of technologies from cell biology to cryogenic electron microscopy, the LMU researchers have revealed how single-stranded foreign RNA is processed to be detected by TLR7. Their work has been published in the journal Immunity.
Numerous enzymes are involved in the recognition of foreign RNA
In the course of evolution, the immune system has specialized in recognizing pathogens from their genetic material. For example, the innate immune receptor TLR7 is stimulated by viral RNA. We can picture viral RNAs as long threads of molecules, which are much too large to be recognized as ligands for TLR7. This is where nucleases come in — molecular cutting tools that chop the ‘RNA thread’ into small pieces. Endonucleases cut the RNA molecules through the middle like scissors, while exonucleases cleave the thread from one end to the other. This process generates various RNA snippets, which can now bind to two different pockets of the TLR7 receptor. Only once both binding pockets of the receptor are occupied by these RNA pieces a signaling cascade set in motion, which activates the cell and triggers a state of alarm.
The researchers discovered that RNA recognition by TLR7 requires the activity of the endonuclease RNase T2 operating in conjunction with the exonucleases PLD3 and PLD4 (phospholipase D3 and D4). “Although it was known that these enzymes can degrade RNAs,” says Hornung, “we have now demonstrated that they interact and thereby activate TLR7.”
Balancing the immune system
The researchers also found that the PLD exonucleases have a dual role within immune cells. In the case of TLR7, they have a pro-inflammatory effect, whereas in the case of another TLR receptor, TLR9, they have an anti-inflammatory effect. “This dual role of PLD exonucleases points to a finely coordinated balance for controlling appropriate immune responses,” explains Bérouti. “The simultaneous promotion and inhibition of inflammation by these enzymes could serve as an important protective mechanism for preventing dysfunctions arising in the system.” What role other enzymes could have on this signaling pathway and whether the molecules involved are suitable as target structures for therapies are subjects for further investigations.

An extensive analytical study conducted at the Terasaki Institute for Biomedical Innovation (TIBI) has revealed an association between favorable survival outcomes for melanoma patients and the presence of higher populations of tissue-resident memory T cells (TRM). Data obtained from this study could be used not only for a TRM-based machine learning model with predictive powers for melanoma prognosis but could also elucidate the role TRM cells can play in the tumor immune microenvironment. This could guide the development of more effective and personalized anti-tumor immunotherapeutic treatment regimens for cancer patients.
The tumor immune microenvironment (TIME) refers to the complex and dynamic interplay between tumor cells, various immune cells, and other cellular and non-cellular components within and surrounding the tumor.
TRM cells are a unique type of immune cells that reside in peripheral tissues and many kinds of cancer types.
Because of the presence and functional properties of TRM cells within the TIME in harnessing their potential for cancer immunotherapy, there has been much interest in studying TRM cells and how they influence patient survival. Key to this understanding is to establish whether the presence and abundance of TRM cells in cancer patients correlate with better patient prognosis. Previous studies conducted with melanoma patients have produced conflicting results. There has also been little effort to conduct a comprehensive study to evaluate the TRM abundance and correlate immunomics data with patient survival outcomes.
The TIBI team sought to solve this problem by turning to data from single-cell RNA sequencing (scRNA-seq), a powerful technology that allows one to obtain a complete genetic profile of large numbers of individual cells. Instead of using a limited number of a cell’s identifying marker genes, utilizing the scRNA-seq technology provides a more comprehensive, accurate, and nuanced way of characterizing a cell’s type and function. From this profile, gene signatures can be generated- uniquely characteristic patterns of a specific immune cell type that can possibly be correlated with the presence of disease.
As described in their recent paper in iScience, the team used this approach on two independent cohorts of melanoma patients’ scRNA-seq data and were able to extract 11 distinct gene signatures that highly correlated with TRM abundance in the patients. A solid association was also found between these gene signatures and patient survival outcomes.
Further studies revealed additional positive correlations between TRM abundance and the presence of multiple anti-tumor immune cells in the melanoma TIME, as well as with immune pathways and regulatory genes, suggesting that TRM cells have a crucial role in immunomodulation. The studies also indicated that an abundance of TRM cells results in a more active melanoma TIME and better patient outcomes.

Finally, the TIBI researchers could use the data from their analysis to create a high-precision TRM-derived risk scoring system to classify patients into high- and low-risk prognostic categories for melanoma patients.
“Our scientists’ analytical approach and discoveries about the role that TRM cells play may help to refine and more accurately assess cancer patients’ response to immunotherapeutic drugs,” said Ali Khademhosseini, TIBI’s Director and CEO. “As treatments can have profoundly variable effects on individual cancer patients, this is an important step toward improving patient outcome.”
Authors: Chongming Jiang, Cheng-Chi Chao, Jianrong Li, Xin Ge, Aidan Shen, Vadim Jucaud, Chao Cheng, and Xiling Shen
Grant Information: This work is supported by the National Institutes of Health, USA (NIH) R01 DK119795 and R35 GM122465. This work is was also funded by the Cancer Prevention Research Institute of Texas (CPRIT) (RR180061).

The length of telomeres in white blood cells, known as leukocytes, varies significantly among sub-Saharan African populations, researchers report May 2nd in The American Journal of Human Genetics. Moreover, leukocyte telomere length (LTL) is negatively associated with malaria endemicity and only partly explained by genetic factors.
“We highlight the contributions of genetic and environmental factors influencing LTL, and we have uncovered a potential role of malaria in shortening LTL across sub-Saharan Africa,” says Sarah Tishkoff of the University of Pennsylvania, a co-senior author on the study. “This association between malaria and LTL appears larger than any other known exposure or behavior that has been investigated in large-scale studies.”
Telomeres are regions of repetitive DNA sequences that protect the ends of chromosomes from becoming frayed or tangled. LTL shows vast person-to-person variation, with individuals of African ancestry generally having longer LTL than non-Africans. It shortens with age and is a predictor of a range of aging-related diseases and mortality. LTL is a highly heritable human trait, and LTL variation at birth largely determines LTL variation throughout the life course.
“However, the majority of large-scale studies examining LTL variation among humans have focused primarily on populations of European ancestry,” Tishkoff says. “This under-representation of diverse populations hampers our ability to understand the genetic and environmental drivers of LTL variation and their effects on telomere-related disease risk.”
In particular, little is known about the genetic, environmental, and evolutionary forces that have shaped the vast LTL variation across sub-Saharan African populations. This variation in LTL is largely explained by genetic factors, but environmental factors could also play a role. Exposure to Plasmodium falciparum malaria is one environmental factor of particular interest in impacting LTL, due to recent studies demonstrating a link between malaria infection and LTL.
While these studies suggest a link between malaria infection and telomere shortening, they rely on single, acute infection events where participants received rapid medical treatment. It remains unknown whether repeated malaria exposures throughout life in populations living in endemic regions has a lasting effect on LTL. It is also unclear whether having longer leukocyte telomeres at birth in malaria endemic regions or regions with a high pathogen burden could be selectively advantageous.
To fill these knowledge gaps, Tishkoff and co-senior study author Abraham Aviv of Rutgers University examined LTL from diverse environmental contexts across Africa, including those where malaria is highly endemic. The authors extracted DNA from blood cells and genotyped individuals and measured LTL in 1,818 ethnically diverse adults from Tanzania, Botswana, Ethiopia, and Cameroon.

The results revealed significant variation in LTL among populations. The San hunter-gatherers from Botswana have the longest leukocyte telomeres, and the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain roughly half of LTL variation among individuals.
Moreover, LTL is shorter in adults indigenous to regions of high malaria endemicity than in those indigenous to regions of low malaria endemicity. The potential impact of malaria endemicity on LTL reported in this study appears larger than previously identified environmental factors that impact LTL. One potential mechanism by which malaria may shorten LTL may involve malaria-induced bouts of massive destruction of erythrocytes (i.e., red blood cells) and the process of making new cells to restore this loss.
“Circulating erythrocytes outnumber circulating leukocytes by approximately a thousand to one and comprise 84% of all somatic cells in the body,” Tishkoff explains. “The telomere length reserves of the hematopoietic system are, thus, principally spent on building and maintaining the massive pool of about 25 trillion erythrocytes in the average human adult.”
The authors say a longitudinal study in children and adults indigenous to regions of high and low malaria endemicity would provide more insightful information. “We propose that the effect of malaria on hematopoietic cell telomere shortening with age primarily unfolds during childhood, yet our LTL data are derived from adults,” Tishkoff says. “Clearly, the next step in testing the relationship between malaria and LTL is to characterize LTL dynamics in children born and raised in regions of high malaria endemicity versus those born and raised in regions of low or no malaria endemicity.”
This research was supported by the National Institutes of Health, an American Diabetes Association Pathway to Stop Diabetes grant, and the Center of Excellence in Environmental Toxicology (CEET) at the University of Pennsylvania.

Genetics can be associated with one’s behavior and health — from the willingness to take risks, and how long one stays in school, to chances of developing Alzheimer’s disease and breast cancer. Although our fate is surely not written in our genes, corporations may still find genetic data valuable for risk assessment and business profits, according to a perspective published on May 2 in The American Journal of Human Genetics. The researchers stress the need for policy safeguards to address ethics and policy concerns regarding collecting genetic data.
At-home DNA tests have provided millions with insights into their family history and health risk by simply spitting in a tube. Genetic risk screening of embryos at in vitro fertilization clinics is now available. These tests rely on polygenic scores — a tally of variations in human genes that influence a certain trait. However, while powerful at predicting traits in large populations, these scores are rather weak at an individual level.
“And for that reason, people have said, ‘we don’t need to worry about companies wanting to use this information at the individual level because it’s not very informative,'” says economist and co-corresponding author Nicholas Papageorge of Johns Hopkins University. “Well, that’s not exactly true. Firms operate under a lot of uncertainty and any little bit of information that they have about you is worthwhile.”
Using an economic model, the researchers found that companies might be willing to pay for a consumer’s polygenic score even if it’s only marginally accurate as a predictor, because the information may raise profit and is relatively cheap. For example, knowing a person’s polygenic score, such as risk of cognitive decline or risky behaviors, an insurance firm may tailor their offerings to individuals, decline insurance, or raise premiums.
“And it might be counterintuitive, but there might be welfare-enhancing uses of such data,” says co-corresponding author, legal scholar, and bioethicist Michelle Meyer of Geisinger College of Health Sciences.
For example, financial service companies may develop products that reduce financial decision-making burdens or offer error monitoring services for people at high polygenic risk of Alzheimer’s. “But I do think it’s fair to say the burden is on the firm to explicate and help develop appropriate guardrails to prevent nefarious uses.”
The researchers argue that current laws and policies are inadequate to address the ethical, privacy, and legal concerns surrounding the potential corporate use of polygenic scores. While the US Genetic Information Nondiscrimination Act prohibits discrimination in health coverage and employment based on genetic information, there are loopholes. The act only covers health insurance, excluding long-term, disability, life, and other insurances. It also doesn’t apply to employers with fewer than 15 people, which accounts for 85% of US companies.
“This is a wake-up call to people and to those who are in a position to act,” says Meyer. “We need to put things in place now — or yesterday.”
“I don’t think people realize that when they give up their genetic information today, they’re not giving it up just for today; they’re giving it up forever,” says Papageorge. “When there’s new science, they know a little bit more about you.”

Medical College of Georgia scientists report that a gene previously implicated in the development of atherosclerotic lesions in coronary arteries could be key to understanding why many people don’t benefit from the most used therapy for neovascular age-related macular degeneration (AMD), a leading cause of blindness.
AMD is a condition characterized by abnormal blood vessel growth in the back of the eye. It is highly prevalent in the elderly and people with diabetes, obesity, and many other chronic metabolic diseases. Excessive vascular growth damages the macula, the part of the eye that translates light into image signals.
Anti-VEGF therapy, which blocks vascular endothelial growth factor and keeps excessive blood vessel growth at bay, is usually the first line of defense.
But that treatment only works well for around a third of patients suffering from this form of AMD, says Dr. Yuqing Huo, MD, PhD, the Director of the Vascular Inflammation Program at MCG’s Vascular Biology Center. “The reason is that the excess vasculature is often accompanied by the growth of fibroblast cells,” he says.
Collagen and many other proteins produced by these fibroblast cells accumulate outside of the vascular cells and eventually lead to fibrosis or scarring in the eye. This keeps the excess vasculature from being suppressed by anti-VEGF treatments. “We show, for the first time in this study, that many fibroblast cells are actually produced by these excessive endothelial cells. We must find a way to prevent this from happening,” Huo says.
He and his team believe the answer lies in targeting the adenosine receptor 2A (Adora2a) — a G-protein-coupled adenosine receptor found in high levels in the brain, immune cells, and blood vessels. Adora2a has been reported to be crucial in modulating inflammation, myocardial oxygen consumption, and coronary blood flow. Adenosine, a metabolite produced by cells under conditions of stress, injuries, and lack of oxygen, can activate Adora2a to protect our body from injury.
But in excess, adenosine can lead to excessive blood vessel growth. In their current research, Huo and his colleagues found a high-level or persistent adenosine-activated Adora2a signal could transform endothelial cells, the luminal cells of the vasculature, into activated fibroblast cells and, eventually, cause fibrosis. Huo and his colleagues hypothesize that blocking this receptor can prevent that from happening.

Using genetically engineered mice that develop fibrosis in the backs of their eyes, researchers delivered an Adora2a agonist (KW6002), which binds to the receptor and blocks its function. “We also studied mice that had Adora2a removed from only the vascular endothelial cells,” says Qiuhua Yang, PhD, a postdoctoral fellow with Huo and the first author on this study. “All of these mice demonstrated decreased fibrosis in the eye.” These novel findings were reported and recently selected as the cover image for Science Translational Medicine.
“We have previously demonstrated that blocking Adora2a can reduce excessive blood vessel growth, which happens in the early stages of AMD,” says Yongfeng Cai, PhD, a postdoctoral fellow in Huo’s lab and a member of the research team. They now have an eye toward generating an antibody that could recognize Adora2A.
“The antibody could be delivered via an injection to the back of the eyes, an approach often used in eye clinics, to block the activation of adenosine to Adora2A,” Huo says. “An antibody could really block both excessive blood vessel growth, the early stage of AMD, and fibrosis, the late stage of AMD. Our findings indicate that blocking Adora2a can certainly target multiple stages of this disease, which might be much more efficient than current treatments.”
This research was supported by a National Institutes of Health K99 award to Dr. Qiuhua Yang and funds from the National Eye Institute.

University of Central Florida College of Medicine researcher Renee Fleeman is on a mission to kill drug-resistant bacteria, and her latest study has identified a therapy that can penetrate the slime that such infections use to protect themselves from antibiotics.
In a study published recently in Cell Reports Physical Science, Fleeman showed that an antimicrobial peptide from cows has potential for treating incurable infections from the bacterium Klebsiella pneumoniae. The bacteria, commonly found in the intestines, is usually harmless. It becomes a health hazard when it enters other parts of the body and can cause pneumonia, urinary tract and wound infections. Those at highest risk include seniors and patients with other health problems such as diabetes, cancer, kidney failure and liver disease. However, younger adults and people without additional health problems can acquire urinary tract and wound infections from the bacteria that cannot be treated by antibiotics available today.
The CDC reports that antibiotic resistant bacteria are a growing global health threat. A 2019 study found that nearly 5 million people died worldwide that year from drug-resistant infections. A large portion of those deaths are attributable to K. pneumoniae because it has a 50% death rate without antibiotic therapy.
These bacteria are more resistant to drugs when they live in a biofilm — microorganisms that stick together and are embedded in a protective slime. Recent studies have shown that 60-80% of infections are associated with bacteria biofilms, which increase their drug resistance.
“It’s Iike a coat that bacteria put around itself,” Fleeman says.
Her research is examining ways to remove the protective coat and expose the bacteria so it can be killed by the body’s immune system or antibiotics that currently cannot pass through the biofilm. Through that research, Fleeman discovered how the peptides made by cows can quickly kill K. pneumoniae.
She determined that the peptides interact with sugar connections that keep the slime intact. She likened the process to cutting into a chain-linked fence. Once multiple chains are cut, the integrity of the slime structure is damaged, and the peptide can enter and destroy the bacteria that are no longer protected.

“Our research has shown polyproline peptide can penetrate and begin to break the slime barrier down in as little as an hour after treatment,” says Fleeman.
The peptide has another advantage — once it breaks through the protective slime barrier, tests showed it killed the bacteria better than antibiotics used as a last resort to treat incurable infections. Peptides kill the bacteria by punching holes in their cell membrane, causing death quickly compared to other antibiotics that inhibit growth from inside the cell.
The peptide could also be used as a topical treatment for a wide range of uses, especially for the military, to treat open wounds in the field. “Bacteria divide every 30 minutes, so you have to act fast,” Fleeman says.
The next phase of her research will seek to understand the biology behind the peptide’s efficacy and if combinations of other drugs would aid in its application.
Her research is funded through a three-year National Institutes of Health funding Pathway to Independence R00 grant and is in its second year. Her study initially started as a K99 award at University of Texas at Austin, where she worked before joining UCF in September of 2022.
Fleeman says research into resistant infections must continue because they pose such a threat to health.
“It is estimated that by 2050, antibiotic resistant bacterial infections will be the number one cause of human deaths,” she says. “Our work is focused on preparing for this post-antibiotic era battle, where common antibiotics that we take for granted will no longer be effective, jeopardizing cancer therapy, organ transplants, and any modern medical advancement that relies on effective antibiotic therapies.”

Many people are afraid of needles, and having a doctor take a blood sample from their arm makes them uncomfortable. There is an alternative: a prick to the fingertip or earlobe. But for many laboratory tests, the drop of blood that can be obtained from these places is not enough. Above all, however, tests done with them are often inaccurate: laboratory values fluctuate from measurement to measurement.
Researchers at ETH Zurich have now developed a new device for taking blood samples. It works according to the leech principle and is less invasive than taking blood from the arm with a needle. It is also easy to handle and can be used by people without medical training. Although the new device cannot collect as much blood as a needle, it can collect significantly more than a finger prick. This makes diagnostic measurements more reliable.
Low risk of injury
The ETH researchers came up with the idea for the new device while previously developing something else: a suction cup that transports medication into the blood via the mucous membrane lining the inside of the mouth. “For this earlier project, we had already studied leeches, which attach to their host with a sucker. We realised that we could develop a similar system to collect blood,” says David Klein, a doctoral student in the group led by Jean-Christophe Leroux, Professor of Drug Formulation and Delivery at ETH Zurich.
After leeches have attached themselves, they penetrate the host’s skin with their teeth. To suck blood from the wound, they create negative pressure by swallowing. The new device works in a very similar way: A suction cup measuring about two and a half centimetres is attached to the patient’s upper arm or back. Within the cup are a dozen microneedles that puncture the skin when pressed against it. Within a few minutes, the negative pressure in the suction cup has ensured that sufficient blood has been collected to be used for diagnostic tests.
The new device is very cost-effective to produce, says Nicole Zoratto, a postdoc in Leroux’s group. She led the work on this development and is lead author of the study published in the journal Advanced Science. Zoratto also sees a future application for the new device in low-income regions such as sub-Saharan Africa, where it could play a major part in the fight against tropical diseases such as malaria. Diagnosing malaria involves taking blood from the patients.
Another advantage of the new device is that the microneedles are located within the suction cup. This minimises the risk of injury during the application and after disposal compared to blood sampling with conventional needles.

In the current version of the leech-like device, the suction cup is made of silicone and the microneedles concealed within are made of steel. However, the researchers are in the process of developing a new version made using fully biodegradable materials to create a sustainable product.
Seeking a partner for market launch
The researchers have tested their new device on pigs, and they have made comprehensive manufacturing information.
Before the device can be widely used on humans — in malaria regions and elsewhere — the material composition still needs to be optimised. And above all, safe use must be tested with a small group of test subjects. As such studies are complex and expensive, the research group is still looking for a partner for further funding, for example a charitable foundation. They hope that their new leech devices will soon be able to play a part in the health of children and anyone else who is afraid of needles.