FAU researchers analyze resistance training in older adults at the cellular level

Aging involves a balance between oxidants and antioxidants, low-grade inflammation, and a protein response that occurs at the cellular level, which is responsible for many health disorders.

Exercise has been shown to regulate the inflammatory response, balance oxidants such as free radicals that build up in the cells and damage DNA; and ameliorate the process by which cells protect themselves against these stressors. Furthermore, resistance training in older adults is recommended to help maintain muscle, flexibility, and balance.  

Aging and related diseases are associated with alterations in oxidative status and low-grade inflammation, as well as a decreased endoplasmic reticulum (ER) unfolded protein response (UPR). UPR is a functional mechanism by which cells attempt to protect themselves against ER stress, resulting from the accumulation of unfolded/misfolded proteins.

One group of proteins associated with the aging process is the mitochondrial heat shock protein 60 (HSP60), which has been demonstrated to play a protective role in the ability of cells to remain active and healthy. Currently, there is limited research investigating the effects of resistance training in older adults on the expression of HSP60 and Klotho, a gene involved in the aging process in mammals.

A new study by researchers at Florida Atlantic University, in collaboration with the University of León in Spain, examined whether an eight-week resistance training program would modulate the oxidative status, the UPR activation, and key inflammatory pathways as well as their relationships with HSP60 and Klotho proteins.

For the study, researchers analyzed these proteins in peripheral blood mononuclear cells of elderly subjects. In addition, they utilized supercomputer simulation to predict the key proteins associated with these biomolecules underlying physiological adaptations to exercise. They collected blood samples approximately five to six days before and after the training period and just before training intervention in young subjects who were included in basal assessments. Researchers also analyzed various oxidative stress biomarkers in peripheral blood mononuclear cells. 

Results of the study, published in the journal Antioxidantsdemonstrated that the levels of the inflammatory proteins (pIRAK1, TLR4, and TRAF6), as well as different markers of the redox balance (catalase, GSH, LP, NRF2, PC, ROS, SOD1, and SOD2) remained unchanged with training. Importantly, untrained elderly subjects showed a significant reduction in pIRE1/IRE1 ratio when compared to trained elderly subjects. Such a finding was further confirmed by a gene ontology analysis, showing that endoplasmic reticulum stress is a key mechanism modulated by IRE1. Additionally, the analysis did not show the training effect on the expression of HSP60 and Klotho or their relationships with other outcome variables. Although elderly male and female subjects were included in the training program, researchers did not find any sex effects in the study. These findings might partially support the modulatory effect of resistance training on the endoplasmic reticulum in the elderly.

“Regular physical activity is suggested to be an effective intervention in improving age-related diseases such as osteoporosis, sarcopenia or muscle loss and dynapenia or loss of muscle strength, cardiovascular diseases, and type 2 diabetes,” said Chun-Jung “Phil” Huang, Ph.D., co-author and a professor in the Department of Exercise Science and Health Promotion within FAU’s Charles E. Schmidt College of Science. “Although the beneficial effects of regular physical exercise to alleviate inflammation and oxidative stress are well-established, the processes of these physiological adaptations with regard to protein folding or UPR remains to be explored. That is why we used a systems biology approach for our study.”

The resistance training protocol for the study consisted of 16 sessions over eight weeks (two sessions per week), with a minimum of 48 hours between sessions. The participants started with a 10-minute warm-up on a cycle ergometer. Subsequently, eight different resistance exercises (leg press, ankle extension, bench press, leg extension, bicep curl, pec deck, high pulley traction, and dumbbell lateral lift) were performed using the exercise device. For each exercise, participants performed three sets of 12-8-12 repetitions. There was a two-to-three-minute rest between each repetition and a three-minute rest between each exercise.

“We know how very important physical activity is for older adults and our study takes research one step further in helping to elucidate the benefits of exercise in this population,” said Huang.

Study co-authors are senior author Brisamar Estébanez, Ph.D.; Marta Rivera-Viloria; and José A. de Paz, M.D., all with the University of León; José E. Vargas, Ph.D., Universidad Federal do Paraná, Curitiba; and Nishant P. Visavadiay, Ph.D.; and Andy V. Kahmoui, Ph.D., both with FAU’s Department of Exercise Science and Health Promotion.  

Two images of a solar active region (NOAA AR 2109) taken by SDO/AIA show extreme-ultraviolet light produced by million-degree-hot coronal gas (top images) on the day before the region flared (left) and the day before it stayed quiet and did not flare (right). The changes in brightness (bottom images) at these two times show different patterns, with patches of intense variation (black & white areas) before the flare (bottom left) and mostly gray (indicating low variability) before the quiet period (bottom right). Credits: NASA/SDO/AIA/Dissauer et al. 2022
Two images of a solar active region (NOAA AR 2109) taken by SDO/AIA show extreme-ultraviolet light produced by million-degree-hot coronal gas (top images) on the day before the region flared (left) and the day before it stayed quiet and did not flare (right). The changes in brightness (bottom images) at these two times show different patterns, with patches of intense variation (black & white areas) before the flare (bottom left) and mostly gray (indicating low variability) before the quiet period (bottom right). Credits: NASA/SDO/AIA/Dissauer et al. 2022

NWRA team's new database makes it easier for scientists to predict solar flares

In the blazing upper atmosphere of the Sun, a team of scientists has found new clues that could help predict when and where the Sun’s next flare might explode.

Using data from NASA’s Solar Dynamics Observatory, or SDO, researchers from NorthWest Research Associates, or NWRA, identified small signals in the upper layers of the solar atmosphere, the corona, that can help identify which regions on the Sun are more likely to produce solar flares – energetic bursts of light and particles released from the Sun.

They found that above the regions about to flare, the corona produced small-scale flashes – like small sparklers before the big fireworks.

This information could eventually help improve predictions of flares and space weather storms – the disrupted conditions in space caused by the Sun’s activity. Space weather can affect Earth in many ways: producing auroras, endangering astronauts, disrupting radio communications, and even causing large electrical blackouts.

Scientists have previously studied how activity in lower layers of the Sun’s atmosphere – such as the photosphere and chromosphere – can indicate impending flare activity in active regions, which are often marked by groups of sunspots, or strong magnetic regions on the surface of the Sun that are darker and cooler compared to their surroundings. The new findings, published in The Astrophysical Journal, add to that picture.

“We can get some very different information in the corona than we get from the photosphere, or ‘surface’ of the Sun,” said KD Leka, lead author on the new study who is also a designated foreign professor at Nagoya University in Japan. “Our results may give us a new marker to distinguish which active regions are likely to flare soon and which will stay quiet over an upcoming period.”

For their research, the scientists used a newly created image database of the Sun’s active regions captured by SDO. The publicly available resource, described in a companion paper also in The Astrophysical Journal, combines over eight years of images taken of active regions in ultraviolet and extreme-ultraviolet light. Led by Karin Dissauer and engineered by Eric L. Wagner, the NWRA team’s new database makes it easier for scientists to use data from the Atmospheric Imaging Assembly (AIA) on SDO for large statistical studies.

“It's the first time a database like this is readily available for the scientific community, and it will be very useful for studying many topics, not just flare-ready active regions,” Dissauer said.

The NWRA team studied a large sample of active regions from the database, using statistical methods developed by team member Graham Barnes. The analysis revealed small flashes in the corona preceded each flare. These and other new insights will give researchers a better understanding of the physics taking place in these magnetically active regions, to develop new tools to predict solar flares.

“With this research, we are starting to dig deeper,” Dissauer said. “Down the road, combining all this information from the surface up through the corona should allow forecasters to make better predictions about when and where solar flares will happen.”

A black hole repeatedly destroying a star

Animation describing the scientific result published here: Wevers, Coughlin, Pasham et al. (2022), https://ui.adsabs.harvard.edu/abs/202... A mysterious flash of electromagnetic radiation from the center of a galaxy some 800 million light years away was first detected in 2018. The flare lasted for about 2 years and then it disappeared. This behavior is consistent with the supermassive black hole a...

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Joachim Kock, Associate Professor at the Department of Mathematics, University of Copenhagen. Photo: Jim Høyer
Joachim Kock, Associate Professor at the Department of Mathematics, University of Copenhagen. Photo: Jim Høyer

University of Copenhagen prof Kock's COVID computations trigger a solution to an old problem in computer science

A mathematician from the University of Copenhagen was keen to forecast the evolvement of the COVID epidemic. Instead, he ended up solving a problem that had troubled computer scientists for decades.

During the corona epidemic, many of us became amateur mathematicians. How quickly would the number of hospitalized patients rise, and when would herd immunity be achieved? Professional mathematicians were challenged as well, and a researcher at the University of Copenhagen became inspired to solve a 30-year-old problem in computer science.

“Like many others, I was out to calculate how the epidemic would develop. I wanted to investigate certain ideas from theoretical computer science in this context. However, I realized that the lack of a solution to the old problem was a showstopper,” says Joachim Kock, Associate Professor at the Department of Mathematics, University of Copenhagen.

His solution to the problem can be of use in epidemiology and computer science, and potentially in other fields as well. A common feature for these fields is the presence of systems where the various components exhibit mutual influence. For instance, when a healthy person meets a person infected with COVID, the result can be two people infected.

The smart method invented by a German teenager

To understand the breakthrough, one needs to know that such complex systems can be described mathematically through so-called Petri nets. The method was invented in 1939 by German Carl Adam Petri (by the way at the age of only 13) for chemistry applications. Just like a healthy person meeting a person infected with COVID can trigger a change, the same may happen when two chemical substances mix and react.

In a Petri net, the various components are drawn as circles while events such as a chemical reaction or an infection are drawn as squares. Next, circles and squares are connected by arrows which show the interdependencies in the system.

Computer scientists regarded the problem as unsolvable

In chemistry, Petri nets are applied for calculating how the concentrations of various chemical substances in a mixture will evolve. This manner of thinking has influenced the use of Petri nets in other fields such as epidemiology: we are starting with a high “concentration” of un-infected people, whereafter the “concentration” of infected starts to rise. In computer science, the use of Petri nets is somewhat different: the focus is on individuals rather than concentrations, and the development happens in steps rather than continuously.

What Joachim Kock had in mind was to apply the more individual-oriented Petri nets from computer science for COVID calculations. This was when he encountered the old problem:

“The processes in a Petri net can be described through two separate approaches. The first approach regards a process as a series of events, while the second approach sees the net as a graphical expression of the interdependencies between components and events,” says Joachim Kock, adding:

“The serial approach is well suited for performing calculations. However, it has a downside since it describes causalities less accurately than the graphical approach. Further, the serial approach tends to fall short when dealing with events that take place simultaneously.”

“The problem was that nobody had been able to unify the two approaches. The computer scientists had more or less resigned, regarding the problem as unsolvable. This was because no one had realized that you need to go back and revise the very definition of a Petri net,” says Joachim Kock.

Small modifications with a large impact

The Danish mathematician realized that a minor modification to the definition of a Petri net would enable a solution to the problem:

“By allowing parallel arrows rather than just counting them and writing a number, additional information is made available. Things work out and the two approaches can be unified.”

The exact mathematical reason why this additional information matters is complex, but can be illustrated by an analogy:

“Assigning numbers to objects has helped humanity greatly. For instance, it is highly practical that I can arrange the right number of chairs in advance for a dinner party instead of having to experiment with different combinations of chairs and guests after they have arrived. However, the number of chairs and guests does not reveal who will be sitting where. Some information is lost when we consider numbers instead of real objects.”

Similarly, information is lost when the individual arrows of the Petri net are replaced by a number.

“It takes a bit more effort to treat the parallel arrows individually, but one is amply rewarded as it becomes possible to combine the two approaches so that the advantages of both can be obtained simultaneously.”

The circle to COVID has been closed

The solution helps our mathematical understanding of how to describe complex systems with many interdependencies, but will not have much practical effect on the daily work of computer scientists using Petri nets, according to Joachim Kock:

“This is because the necessary modifications are mostly back-compatible and can be applied without the need for revision of the entire Petri net theory.”

“Somewhat surprisingly, some epidemiologists have started using the revised Petri nets. So, one might say the circle has been closed!”

Joachim Kock does see a further point to the story:

“I wasn’t out to find a solution to the old problem in computer science at all. I just wanted to do COVID calculations. This was a bit like looking for your pen but realizing that you must find your glasses first. So, I would like to take the opportunity to advocate the importance of research that does not have a predefined goal. Sometimes research driven by curiosity will lead to breakthroughs.”

Syracuse physicist Coughlin builds a model that maps a star’s surprising orbit around a supermassive black hole

Hundreds of millions of light-years away in a distant galaxy, a star orbiting a supermassive black hole is being violently ripped apart under the black hole’s immense gravitational pull. As the star is shredded, its remnants are transformed into a stream of debris that rains back down onto the black hole to form a very hot, very bright disk of material swirling around the black hole, called an accretion disc. This phenomenon – where a star is destroyed by a supermassive black hole and fuels a luminous accretion flare – is known as a tidal disruption event (TDE), and it is predicted that TDEs occur roughly once every 10,000 to 100,000 years in a given galaxy. 

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With luminosities exceeding entire galaxies (i.e., billions of times brighter than our Sun) for brief periods (months to years), accretion events enable astrophysicists to study supermassive black holes (SMBHs) from cosmological distances, providing a window into the central regions of otherwise-quiescent - or dormant - galaxies. By probing these "strong-gravity’’ events, where Einstein's general theory of relativity is critical for determining how matter behaves, TDEs yield information about one of the most extreme environments in the universe: the event horizon – the point of no return – of a black hole. This illustration depicts a star (in the foreground) experiencing spaghettification as it’s sucked in by a supermassive black hole (in the background) during a ‘tidal disruption event’. Credit: ESO/M. Kornmesser

TDEs are usually “once-and-done” because the extreme gravitational field of the SMBH destroys the star, meaning that the SMBH fades back into darkness following the accretion flare. In some instances, however, the high-density core of the star can survive the gravitational interaction with the SMBH, allowing it to orbit the black hole more than once. Researchers call this a repeating partial TDE.

A team of physicists, including lead author Thomas Wevers, Fellow of the European Southern Observatory, and co-authors Eric Coughlin, assistant professor of physics at Syracuse University, and Dheeraj R. “DJ” Pasham, a research scientist at MIT’s Kavli Institute for Astrophysics and Space Research, have proposed a model for a repeating partial TDE. Their findings, published in The Astrophysical Journal Letters, describe the capture of the star by an SMBH, the stripping of the material each time the star comes close to the black hole, and the delay between when the material is stripped and when it feeds the black hole again. The team’s work is the first to develop and use a detailed model of a repeating partial TDE to explain the observations, make predictions about the orbital properties of a star in a distant galaxy, and understand the partial tidal disruption process.

On a Collision Course with a Black Hole

The team is studying a TDE known as AT2018fyk (AT stands for "Astrophysical Transient’’). The star was captured by an SMBH through an exchange process known as “Hills capture,” where the star was originally part of a binary system (two stars that orbit one another under their mutual gravitational attraction) that was ripped apart by the gravitational field of the black hole. The other (non-captured) star was ejected from the center of the galaxy at speeds comparable to ~ 1000 km/s, which is known as a hypervelocity star.

Once bound to the SMBH, the star powering the emission from AT2018fyk has been repeatedly stripped of its outer envelope each time it passes through its point of closest approach with the black hole. The stripped outer layers of the star form the bright accretion disk, which researchers can study using X-Ray and Ultraviolet /Optical telescopes that observe light from distant galaxies.

According to Wevers, having the opportunity to study a repeating partial TDE gives unprecedented insight into the existence of supermassive black holes and the orbital dynamics of stars in the centers of galaxies.

“Until now, the assumption has been that when we see the aftermath of a close encounter between a star and a supermassive black hole, the outcome will be fatal for the star, that is, the star is destroyed,” he says. “But contrary to all other TDEs we know of when we pointed our telescopes to the same location again several years later, we found that it had re-brightened again. This led us to propose that rather than being fatal, part of the star survived the initial encounter and returned to the same location to be stripped of material once more, explaining the re-brightening phase.”

Living to Die Another Day

First detected in 2018, AT2018fyk was initially perceived as an ordinary TDE. For approximately 600 days the source stayed bright in the X-ray, but then abruptly went dark and was undetectable - a result of the stellar remnant core returning to a black hole, explains MIT physicist Dheeraj R. Pasham.

“When the core returns to the black hole it essentially steals all the gas away from the black hole via gravity and as a result, there is no matter to accrete and hence the system goes dark,” Pasham says.

It wasn’t immediately clear what caused the precipitous decline in the luminosity of AT2018fyk because TDEs normally decays smoothly and gradually – not abruptly – in their emission. But around 600 days after the drop, the source was again found to be X-ray bright. This led the researchers to propose that the star survived its close encounter with the SMBH for the first time and was in orbit about the black hole.

Using supercomputer modeling, the team’s findings suggest that the orbital period of the star about the black hole is roughly 1,200 days, and it takes approximately 600 days for the material that is shed from the star to return to the black hole and start accreting. Their model also constrained the size of the captured star, which they believe was about the size of the sun. As for the original binary, the team believes the two stars were extremely close to one another before being ripped apart by the black hole, likely orbiting each other every few days.

So how could a star survive its brush with death? It all comes down to a matter of proximity and trajectory. If the star collided head-on with the black hole and passed the event horizon – the threshold where the speed needed to escape the black hole surpasses the speed of light – the star would be consumed by the black hole. If the star passed very close to the black hole and crossed the so-called "tidal radius" – where the tidal force of the hole is stronger than the gravitational force that keeps the star together – it would be destroyed. In the model they have proposed, the star's orbit reaches a point of closest approach that is just outside of the tidal radius, but doesn't cross it completely: some of the material at the stellar surface is stripped by the black hole, but the material at its center remains intact.

A Repeat Performance?

How, or if, the process of the star orbiting the SMBH can occur over many repeated passages is a theoretical question that the team plans to investigate with future simulations. Syracuse physicist Eric Coughlin explains that they estimate between 1 to 10% of the mass of the star is lost each time it passes the black hole, with the large range due to uncertainty in modeling the emission from the TDE.

“If the mass loss is only at the 1% level, then we expect the star to survive for many more encounters, whereas if it is closer to 10%, the star may have already been destroyed,” notes Coughlin.

The team will keep their eyes on the sky in the coming years to test their predictions. Based on their model, they forecast that the source will abruptly disappear around March 2023 and brighten again when the freshly stripped material accretes onto the black hole in 2025.

The Future of TDE Research

The team says their study offers a new way forward for tracking and monitoring follow-up sources that have been detected in the past. The work also suggests a new paradigm for the origin of repeating flares from the centers of external galaxies.

“In the future, it is likely that more systems will be checked for late-time flares, especially now that this project puts forth a theoretical picture of the capture of the star through a dynamical exchange process and the ensuing repeated partial tidal disruption,” says Coughlin. “We’re hopeful this model can be used to infer the properties of distant supermassive black holes and gain an understanding of their 'demographics,' being the number of black holes within a given mass range, which is otherwise difficult to achieve directly.”

The team says the model also makes several testable predictions about the tidal disruption process, and with more observations of systems like AT2018fyk, it should give insight into the physics of partial tidal disruption events and the extreme environments around supermassive black holes.

“This study outlines a methodology to potentially predict the next snack times of supermassive black holes in external galaxies,” says Pasham. “If you think about it, it is pretty remarkable that we on Earth can align our telescopes to black holes millions of light years away to understand how they feed and grow.”