Scientists have now identified a protein pathway that may help connect aging with the harmful protein buildup seen in disorders such as Huntington’s disease and amyotrophic lateral sclerosis (ALS).

Searching for the Link Between Aging and Brain Disease

A research team led by Professor Dr. David Vilchez at the CECAD Cluster of Excellence for Aging Research investigated this connection using the small nematode worm Caenorhabditis elegans. The researchers examined a signaling pathway that becomes increasingly active with age and contributes to the accumulation of abnormal proteins.

Their study, titled “The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation,” was published in Nature Aging.

The team concentrated on EPS8, an aging-associated protein, and the signaling pathways it controls. Previous research showed that EPS8 accumulates as worms grow older and activates damaging stress responses that shorten their lifespan.

EPS8 Drives Toxic Protein Buildup

The researchers found that higher EPS8 levels and increased activity in its signaling pathways promote pathological protein aggregation and neurodegeneration. Both are defining features of age-associated neurodegenerative conditions, including Huntington’s disease and ALS.

When the scientists reduced EPS8 activity, toxic protein aggregates no longer accumulated as readily. The treatment also helped preserve neuronal function in worm models of both diseases.

“We are delighted to uncover a molecular mechanism that could shed light on to how aging contributes to diseases like ALS and Huntington’s,” says first author Dr. Seda Koyuncu. “For years, we’ve known that age is the major common risk factor for different neurodegenerative diseases. However, how exactly age-related changes contribute to these diseases remains largely unknown. This study may contribute to filling in a part of that puzzle.”

Similar Results in Human Cells

EPS8 and the signaling molecules associated with it have been preserved throughout evolution and are also found in human cells. This allowed the researchers to determine whether the mechanism they observed in worms might also be relevant to human disease.

Reducing EPS8 levels in human cell models of Huntington’s disease and ALS produced results similar to those seen in C. elegans. The intervention prevented the accumulation of toxic protein aggregates in the cells.

“It’s incredibly exciting that the mechanisms we uncovered in C. elegans are also conserved in human cell models,” says Professor Dr. David Vilchez, highlighting how the use of simpler model organisms like the nematode worm can prove extremely useful to uncover disease mechanisms relevant to humans.

A Potential Target for Future Treatments

Scientists still do not know precisely how increased EPS8 activity causes toxic proteins to aggregate. Even so, the results address an important gap in neurodegenerative disease research by identifying a direct molecular connection between aging and neurodegeneration.

The findings also point to EPS8 and its signaling partners as possible targets for future therapies. Treatments aimed at this pathway could potentially slow or prevent the progression of ALS, Huntington’s disease, and other brain disorders associated with aging.

“Alzheimer’s is a condition that remains recalcitrant to the scientific community’s attempts at developing a cure or preventative treatment,” said Daniel Schultz, a former postdoctoral fellow in the Vanderbilt University Warren Center for Neuroscience Drug Discovery.

Gaps in Alzheimer’s Biology

One major obstacle to developing better therapies is that researchers still do not fully understand the biology behind Alzheimer’s disease. The same problem affects research into many other neurological diseases and neurodevelopmental disorders.

Scientists have identified genes and proteins that may contribute to these conditions, but studying them can be extremely difficult when researchers lack a reliable way to change how those biological targets behave.

One approach involves using tool compounds. These chemicals interact with particular proteins and either raise or reduce their activity. Although many tool compounds are unsuitable for use as medicines because they may affect unintended targets or cause toxicity, they are still highly valuable for investigating what a protein does. That knowledge can become an important early step toward developing new treatments.

Targeting the TAOK1 Protein

In a study published in ACS Chemical Neuroscience, Schultz and co-first author Lauren Parr, a Ph.D. student in the Department of Pharmacology, developed a compound that selectively inhibits TAOK-1. The protein has been linked to Alzheimer’s disease, but it has remained poorly understood partly because researchers have lacked suitable compounds for studying it.

Most of the work was carried out at the WCNDD under the leadership of Executive Director Craig Lindsley. The WCNDD is a clinical-stage biotech start-up within Vanderbilt. Its drug discovery pipeline currently includes five compounds in phase I clinical trials.

The center is also a founding pillar of the new Vanderbilt Institute for Therapeutic Advances, a next-generation drug discovery institute that is also led by Lindsley.

To find useful compounds, Schultz, Parr, and other WCNDD researchers created a large collection of related molecules. Each one had a slightly different structure. The team then evaluated how the compounds affected TAOK-1 and assessed whether they had properties considered desirable in potential drugs.

“This project showcased the strength of the WCNDD’s drug discovery infrastructure,” Schultz said.

The First Selective TAOK1 Inhibitor

The collaboration led to the discovery of VU6083859, the first selective inhibitor of TAOK-1. The compound could provide a starting point for research aimed at developing future Alzheimer’s disease treatments.

Another molecule produced an unexpected result. The compound, named VU6080195, activated all three proteins in the TAOK family rather than inhibiting them.

“Our understanding of TAOK proteins largely centers around their inhibition, so we are excited at the prospect of studying the neurological effects of increasing their activity,” Schultz said. “As scientists, we can get lost in planning our projects to the last detail and expecting things to go a certain way, so it was quite fun to see this unexpected result.”

Schultz hopes the two compounds will encourage more researchers to investigate the TAOK protein family. So far, these proteins have received relatively little attention in in vivo models.

New Tools for Alzheimer’s Research

A deeper understanding of disease biology can improve the chances of finding effective treatments. With these two compounds now available, neuroscientists can examine how the TAOK protein family functions and explore its links to Alzheimer’s and other neurological diseases.

The findings could eventually help researchers identify new treatment strategies and perhaps contribute to the long-term search for a cure.

The paper “Discovery of VU6083859, a TAOK1 Selective Inhibitor, and VU6080195, a pan-TAOK Activator” was published in ACS Chemical Neuroscience.

The research used funding from the William K. Warren Foundation and received support from the Zenobia and Mark Godschalk Alzheimer’s Research Endowment, the Helen H. and Morris D. Hartman, MD 1910, Neurological Research Fund, the Warren Center for Neuroscience Drug Discovery, and the Vanderbilt Institute for Therapeutic Advances.

A new study in the Journal of Cosmology and Astroparticle Physics (JCAP) examined what would happen if dark matter experienced an additional attractive force. The results were surprisingly counterintuitive. Although the force causes dark matter to gather more efficiently, it usually does not accelerate the growth of cosmic structure. Instead, it tends to slow that growth.

Why Scientists Are Considering a Dark Force

Interest in a possible “dark force” has increased as highly precise observations of the Universe have produced results that do not always align perfectly.

Measurements of cosmic expansion and the development of galaxies and other large structures sometimes appear to tell slightly different stories. Some observations of the distant Universe suggest that expansion may have proceeded somewhat more slowly in the past than the standard cosmological model predicts.

At the same time, studies of the cosmic microwave background have long suggested that matter could be more tightly clustered across the largest scales of the Universe than expected.

These differences are relatively small, but they have encouraged scientists to ask whether the standard model of cosmology may be missing an important ingredient.

One possibility is that dark matter particles feel an extra force that ordinary matter cannot detect. Because the interaction would operate only within the dark matter sector, researchers refer to it as a “dark force.” Such an interaction could potentially affect both the Universe’s expansion and the formation of galaxies and larger cosmic structures.

“What we really know about dark matter has so far been learned only through its gravitational effects,” says Zachary Weiner, a researcher at the Perimeter Institute for Theoretical Physics, corresponding author for the study. “That leaves open the possibility that dark matter might have additional interactions that are hidden from ordinary matter.”

Testing a Force Beyond Gravity

The research team investigated a group of theoretical models in which dark matter particles interact through a long-range force in addition to gravity.

Using theoretical calculations together with cosmological data, the scientists studied how this hidden interaction would influence the history of cosmic expansion and the growth of large-scale structure.

At first, the expected result seems straightforward. If dark matter particles attract each other through another force, they should assemble into clumps more quickly. That stronger clustering might also appear to explain observations suggesting that the Universe contains denser structures than predicted.

“The first thing you would expect is that giving dark matter an additional attractive force should make structures grow faster,” says Weiner. “But another effect comes into play at the same time.”

A Surprising Effect on Cosmic Growth

In the models examined by the researchers, the extra force does make dark matter cluster more effectively. However, it also changes how dark matter behaves as the Universe expands.

The same process causes dark matter particles to effectively lose mass over time. This reduction weakens their gravitational influence, offsetting the stronger attraction produced by the hidden force.

As a result, the enhanced clustering does not create a stronger gravitational imprint on the cosmic microwave background. In most cases, the combined effect actually suppresses the growth of cosmic structure.

Implications for DESI and Dark Energy Models

The findings could matter for theories that extend beyond dark matter alone. Some explanations proposed for recent measurements from the Dark Energy Spectroscopic Instrument (DESI) involve similar interactions among dark matter particles.

According to the researchers, the newly identified mechanism is likely to influence many of those more complicated models as well. Any theory involving a hidden attractive force may need to account for the possibility that dark matter becomes effectively lighter as the Universe evolves.

More precise measurements from upcoming observatories and cosmic surveys could help scientists determine which hidden interactions dark matter might possess and which possibilities observations can rule out.

“The Universe is often more subtle than our intuition,” says Weiner. “That’s exactly why we have to keep testing these ideas.”

The findings support once weekly brisk interval walking as a practical therapeutic option for adults with central obesity, especially those who have difficulty fitting several workouts into their schedules. The study was published in Nature Communications.

A More Practical Approach to Reducing Body Fat

Obesity is a chronic health condition involving an unhealthy buildup of body fat. Fat that accumulates around the abdomen is especially concerning because it is associated with cardiovascular disease, metabolic disorders, and a higher risk of premature death.

Exercise plays an important role in managing obesity and offers a wide range of health benefits. Even so, many people, particularly those living with obesity, struggle to maintain regular physical activity over time.

Interval training alternates between more vigorous periods of exercise and lower-intensity periods of active recovery. Research has shown that it can be a time-efficient way to reduce overall body fat and visceral fat compared with continuous exercise performed at a moderate intensity.

Most exercise recommendations call for interval training three days each week. That schedule may be difficult for people with demanding jobs, family responsibilities, limited time, or restricted access to exercise facilities.

Previous research has suggested that a “weekend warrior” pattern, in which most weekly exercise is completed over one or two days, can still produce health benefits. However, there has been relatively little evidence showing whether interval training remains effective when concentrated into a single weekly session.

Professor Parco Siu Ming-fai, Professor and Head of Division of Kinesiology at the School of Public Health, HKUMed, said it was important to determine whether once weekly interval training could match the results of a traditional three-session schedule and provide a more accessible alternative.

One Session Versus Three

From September 2021 to September 2024, the HKUMed team carried out a randomized trial in Hong Kong involving 315 Chinese adults aged 18 or older. All participants were overweight and had central obesity.

Participants were assigned to one of three groups. One group completed interval training once each week, another completed interval training three times each week, and the third served as a control group.

The control group took part in a 2.5-hour health education session every two weeks for four months. Both exercise groups completed a total of 75 minutes of interval training each week. One group performed the full amount in a single session, while the other divided it across three sessions.

Researchers measured body fat using dual-energy X-ray absorptiometry at three stages: before the program began (baseline), after 16 weeks (post-intervention), and at 32 weeks (four-month post-intervention follow-up).

Similar Fat Loss and Fitness Benefits

At the 16-week assessment, both interval training groups showed similar improvements. Participants who exercised once per week and those who exercised three times per week reduced total body fat mass, body fat percentage, and waist circumference. Both groups also improved their cardiorespiratory fitness compared with the control group.

“While thrice-weekly interval training remains a commonly recommended approach for the therapeutic management of excess adiposity, our findings show that once-weekly interval training offers similar benefits and represents a practical exercise strategy,” said Professor Siu. “For many adults with central obesity who struggle to balance work, study, family and other commitments, time constraints are a primary barrier to exercising multiple days per week.”

“Instead of relying solely on high-frequency exercise prescriptions, once-weekly interval training can be considered a feasible and effective alternative,” added Professor Siu.

The study was led by Professor Parco Siu Ming-fai, Professor and Head of Division of Kinesiology at the School of Public Health, HKUMed. The co-first authors were Dr. Leung Chit-kay and Mr. Joshua Bernal, both from the same School.

The research was supported by the General Research Fund of the Research Grants Council, the University Grants Committee of Hong Kong, China, and the Seed Fund for Basic Research, HKU.

Over the past decade, global temperatures have risen at an estimated pace of about 0.35°C per decade, depending on the dataset used. By comparison, the average warming rate from 1970 to 2015 was just under 0.2°C per decade. The recent pace is higher than that of any previous decade since instrumental temperature records began in 1880.

Scientists Isolate the Long-Term Warming Signal

“We can now demonstrate a strong and statistically significant acceleration of global warming since around 2015,” says Grant Foster, a US statistics expert and co-author of the study, which was published today in the scientific journal Geophysical Research Letters.

“We filter out known natural influences in the observational data, so that the ‘noise’ is reduced, making the underlying long-term warming signal more clearly visible,” Foster added.

In climate data, “noise” refers to short-erm temperature changes that can temporarily hide or exaggerate the underlying trend. El Niño, for example, can push global temperatures higher for a limited period by releasing heat from the tropical Pacific Ocean into the atmosphere. Volcanic eruptions can have the opposite effect by sending particles into the atmosphere that reflect sunlight, while changes in the Sun’s activity can also produce smaller temperature variations.

To separate these temporary influences from the broader warming trend, the researchers analyzed measurements from five widely used global temperature data sets (NASA, NOAA, HadCRUT, Berkeley Earth, ERA5).

“The adjusted data show an acceleration of global warming since 2015 with a statistical certainty of over 98 percent, consistent across all data sets examined and independent of the analysis method chosen,” explains Stefan Rahmstorf, PIK researcher and lead author of the study.

Warming Acceleration Appears Across Five Datasets

A statistical certainty of more than 98 percent means the researchers found strong evidence that the change in the warming rate is real rather than the result of random variation in the data. The same overall pattern appeared in all five temperature records, even though the datasets are produced by different scientific organizations and use somewhat different methods.

After the researchers adjusted for El Niño and the solar maximum, the extreme warmth of 2023 and 2024 was reduced slightly in the analysis. Even so, both years remained the two warmest since instrumental records began.

Across all of the datasets, the acceleration started to become visible in 2013 or 2014. The researchers describe the broader shift as beginning around 2015, when the evidence became clearer.

Two Statistical Methods Point to the Same Shift

To determine whether the warming rate had changed since the 1970s, the team used two statistical approaches. The first was a quadratic trend analysis, which tests whether the temperature curve is bending upward over time rather than rising at a constant rate.

The second was a piecewise linear model. This method divides the temperature record into separate periods and objectively identifies when the rate of warming appears to change. Both approaches supported the conclusion that global warming has accelerated.

Study Does Not Identify the Cause

The research was designed to detect and measure the statistical acceleration, not to determine exactly why it has occurred.

However, the authors noted that climate models can produce periods in which warming speeds up. In other words, an increasing rate of warming is consistent with the range of behavior represented in current climate modeling.

Climate models are computer simulations that use the laws of physics to estimate how the atmosphere, oceans, ice, and land respond to greenhouse gases and other influences. They do not predict every short-term fluctuation perfectly, but they help scientists evaluate long-term climate patterns and possible future changes.

1.5°C Threshold Could Be Exceeded Before 2030

“If the warming rate of the past 10 years continues, it would lead to a long-term exceedance of the 1.5°C limit of the Paris Agreement before 2030,” says Stefan Rahmstorf. “How quickly the Earth continues to warm ultimately depends on how rapidly we reduce global CO2 emissions from fossil fuels to zero.”

The 1.5°C limit refers to the goal of restricting long-term global warming to 1.5°C above preindustrial temperatures. A single year above that level does not by itself mean the Paris Agreement threshold has been permanently crossed. Scientists generally focus on sustained warming over a longer period.

The findings suggest that Earth may now be warming considerably faster than it did during the final decades of the 20th century. Whether that acceleration continues will depend heavily on future carbon dioxide emissions from coal, oil, and natural gas.