Published in Nature Communications, the study provides the first randomized, placebo-controlled evidence in humans that semaglutide may slow the buildup of DNA markers linked to biological aging in adults living with HIV.

Semaglutide Slowed Biological Aging Markers

Scientists from the University of California San Diego and collaborating institutions examined data from an earlier clinical trial involving 108 adults with HIV-associated lipohypertrophy, a condition that causes excess fat to accumulate around the abdomen. Roughly half of the participants received weekly semaglutide injections, while the rest were given a placebo for comparison.

To evaluate aging, the researchers relied on several “epigenetic clocks.” These tools estimate biological age by measuring DNA methylation, a pattern of chemical tags that influences how genes are switched on or off without changing the DNA sequence itself. Changes in these markers can provide insight into whether the body’s cells appear to be aging faster or more slowly than expected.

People living with HIV often experience accelerated biological aging, even when the virus is well controlled with modern antiretroviral therapy, explained first author Michael Corley, PhD, an associate professor at the UC San Diego School of Medicine and the Stein Institute for Research on Aging.

Compared with participants who received placebo injections, those treated with semaglutide showed:

• Slower biological aging across multiple epigenetic clocks tied to inflammation and the health of the blood, brain, heart, kidneys, liver, and metabolism.
• A 9% slower pace of biological aging based on the DunedinPACE epigenetic clock.
• A significant slowing of biological processes linked to age-related disease and all-cause mortality risk, as measured by the PCGrimAge epigenetic clock.

Why Could GLP-1 Drugs Affect Aging?

Researchers believe semaglutide may influence aging through several interconnected pathways.

GLP-1 medications reduce inflammation and improve metabolic health, which can decrease chronic immune activation, one of the major drivers of accelerated aging in people with HIV. They also reduce visceral fat, the fat stored deep around internal organs, as well as ectopic fat that accumulates in places where fat does not normally belong. Lower levels of these harmful fat deposits may reduce inflammatory signals that contribute to aging throughout the body.

“Emerging data also suggest that GLP-1 drugs may reprogram certain cells in different organs, which could help explain why we see effects across multiple aging clocks,” said Corley.

Findings Could Extend Beyond People With HIV

Although the research focused on people with HIV-associated lipohypertrophy, the investigators believe the findings could have broader implications.

“Many of the biological processes we study in HIV are also central to aging in the general population,” said Corley. “Because these processes can emerge earlier or be more pronounced in people with HIV, this community can help us identify interventions that may improve healthspan more broadly.”

Healthspan refers to the number of years a person remains healthy and free from major age-related disease, rather than simply how long they live.

Related Study Found More Signs of Slower Aging

The team also pointed to a pilot study published last month in npj Aging, which examined semaglutide treatment over 24 weeks in people with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD), also known as fatty liver disease.

That study found:

• Biological aging slowed in 42% of participants, based on the DunedinPACE epigenetic clock. Those individuals also experienced greater reductions in liver fat than participants whose biological aging accelerated.
• Aging linked to all-cause mortality risk slowed in 34% of participants, according to the PCGrimAge epigenetic clock.
• Nearly 49% of participants showed longer telomeres, the protective DNA caps at the ends of chromosomes, as measured by the PCDNAmTL epigenetic clock. Those participants also tended to walk faster after treatment, suggesting improvements in physical function.

Together, the two studies add to growing evidence that GLP-1 medications may affect biological pathways involved in aging.

Scientists Urge Caution

Despite the promising findings, the researchers emphasize that semaglutide is not an anti-aging drug.

“We are not saying that semaglutide reverses aging or makes people younger,” said Corley. “What we are seeing is a signal that it may slow some of the biological processes associated with aging. With newer GLP-1-based therapies now emerging, the field has an opportunity to test whether different drugs in this class have distinct effects on aging biology and to identify which patients may benefit most.”

Much larger clinical trials will be needed to confirm the results, determine how long any benefits last, and identify the most effective treatment schedules for both people with HIV and the broader population. Researchers also want to investigate whether combining GLP-1 medications with healthy habits such as diet, exercise, and quality sleep could produce even greater effects on biological aging.

Looking ahead, the Stein Institute for Research on Aging hopes to use these findings to develop personalized “aging dashboards” based on epigenetic clocks. The goal is to help clinicians monitor biological aging more precisely and design individualized treatments that target the underlying causes of age-related disease.

The Nature Communications study was funded in part by the National Institutes of Health (grants P30 AI036214, R01DK121619 and UM1TR004528) and the James B. Pendleton Charitable Trust. The related npj Aging study was also supported in part by the National Institutes of Health (grants P30 AI036214, UM1 AI068634, UM1 AI068636, UM1 AI106701) and the James B. Pendleton Charitable Trust.

Corley serves as a scientific advisor for TruDiagnostic.

Perseverance covered the marathon distance after five years and four months of driving, reaching the mark on the 1,890th Martian day, or sol, of its mission. That pace far surpassed NASA’s previous record holder, the Opportunity rover, which needed 11 years and two months to travel the same distance.

HiRISE Captures Perseverance From Orbit

The striking overhead image was taken by NASA’s Mars Reconnaissance Orbiter (MRO) using its High-Resolution Imaging Science Experiment (HiRISE) camera. Along with the rover itself, the image clearly reveals the winding tracks Perseverance has left behind as it explores the Martian surface.

At the time the image was captured, the rover was operating west of Jezero Crater in a region the mission’s science team has nicknamed “Arbot.”

The Teams Behind the Mission

NASA’s Jet Propulsion Laboratory (JPL) in Southern California, which is managed for NASA by Caltech, oversees operations for both Perseverance and the Mars Reconnaissance Orbiter on behalf of the agency’s Science Mission Directorate as part of the Mars Exploration Program.

Lockheed Martin Space in Denver built the Mars Reconnaissance Orbiter and continues to support its operations. The University of Arizona in Tucson operates the HiRISE camera, which was built by BAE Systems in Boulder, Colorado.

The findings add to growing evidence that consistently getting enough sleep may play an important role in preventing weight gain and lowering the risk of obesity related diseases.

“Our study shows that getting adequate sleep may help reduce the risk of weight gain and obesity-related conditions like heart disease and diabetes,” says Marie-Pierre St-Onge, a professor of nutritional medicine in Columbia’s Department of Medicine and Institute for Human Nutrition and study leader. “People tend to gain weight over the course of their adulthood, and obesity is a major risk factor for heart disease. But focusing on eating a healthier diet and getting more physical activity to offset weight gain is simplistic and can be difficult to maintain.”

Looking Beyond Extreme Sleep Deprivation

Much of the previous research connecting poor sleep with obesity has focused on severe sleep deprivation, often limiting people to only four hours of sleep. Those studies have shown that extreme sleep loss can increase appetite and overeating, factors that contribute to weight gain.

However, such severe sleep restriction is difficult for most people to tolerate for more than a few days.

“These studies only show us what happens under the most extreme conditions and don’t tell us if mildly sleep-deprived people, like a lot of Americans who get 5 or 6 hours of sleep a night, will gain weight,” St-Onge says.

To better reflect real life, the researchers examined the effects of chronic, mild sleep loss, a pattern experienced by roughly 30% of adults.

Six Weeks of Less Sleep Led to Measurable Changes

The study included 95 adults who normally slept between 7 and 8 hours each night. During one six week study period, participants delayed their usual bedtime by 90 minutes. During another six week period, they followed their normal sleep schedule.

Throughout both phases, participants wore wrist monitors that tracked sleep and physical activity. Researchers also measured body weight, waist circumference, body composition, and fasting levels of several hormones involved in appetite regulation.

“While the one-pound weight gain observed with modest sleep curtailment is not overwhelming, it is important to remember this is occurring over just six weeks,” says Faris Zuraikat, assistant professor of nutritional medicine in Columbia’s Department of Medicine and Institute for Human Nutrition and first author of the study. “Our study was designed to mimic sleep patterns that most adults experience chronically. When extrapolated to a full year, we would expect that losing less than an hour and a half of sleep per night could result in clinically meaningful weight gain.”

Less Sleep Also Meant More Sitting

The researchers found that participants became less active during the sleep restriction phase. On average, sedentary time increased by 17 minutes per day. Among men and postmenopausal women, inactivity rose by nearly 30 minutes each day.

“Even when we accounted for the fact that they were awake longer when sleep was shortened, participants spent more time being inactive than when they got adequate sleep,” Zuraikat says. “This is notable, as people who are more sedentary have elevated risk for chronic diseases.”

Earlier Research Suggests Broader Health Effects

The same group of participants has also been examined in related studies. In one previous investigation, women with increased cardiometabolic risk who reduced their sleep by about 80 minutes each night for six weeks developed greater insulin resistance, an important risk factor for type 2 diabetes. The effect was especially pronounced in postmenopausal women.

Another study found that men and women with elevated heart disease risk developed an influx of inflammatory cells in the heart after experiencing mild sleep restriction.

“Though more research is needed to further understand how sleep restriction leads to weight gain, all of our findings suggest that insufficient sleep increases the risk of obesity-related conditions like type 2 diabetes and heart disease,” St-Onge says.

“Now we need to understand the health effects of improving sleep in those who fail to get adequate sleep on a regular basis.”

The study, titled “Skimping on Sleep and Its Impact on Body Weight and Composition: A Pooled Analysis of Randomized Trials,” was published on July 6 in Annals of Internal Medicine.

The authors are Faris Zuraikat, Samantha Scaccia, Justin Cochran, Bin Cheng, Keith Diaz, Seth Creasy (University of Colorado), Brooke Aggarwal, Sanja Jelic, and Marie-Pierre St-Onge.

The authors report no conflicts of interest.

The research was supported by the American Heart Association (16SFRN27950012) and the National Institutes of Health (R01 HL128226, UL1 TR001873, P30 DK026687, R01 HL173190, R01 HL155190, R01 HL153642, K01 HL145023, R01 HL169991, R01 HL106041, R35 HL155670, R01 AG071032, R56 DK136601, P30 DK048520, and R01 DK128154).

Black holes are among the most extreme objects in the known universe. They squeeze enormous amounts of mass into an incredibly small region, creating gravity so intense that not even light can escape. To understand these cosmic objects, physicists rely on Einstein’s theory of general relativity and quantum mechanics.

In the early 1970s, Stephen Hawking and other researchers discovered surprising connections between the laws of thermodynamics, which describe familiar processes such as heating water on a stove, and the behavior of black holes.

“Hawking’s laws of black hole mechanics provided a satisfying connecting between extreme and ordinary physics and have been the paradigm for 50 years, but they have a serious limitation,” said Abhay Ashtekar, Atherton University Professor and Evan Pugh Professor of Physics Emeritus in the Eberly College of Science at Penn State and the leader of the research team. “They were formulated for black holes at equilibrium, or unchanging over time, but black holes are constantly changing, they form, merge and eventually evaporate. We wanted to find a way to overcome this limitation and extend the laws to black holes that are out of equilibrium.”

Ashtekar and his colleagues have now proposed a new method for determining a black hole’s entropy, a quantity that measures disorder and, according to the second law of thermodynamics, can never decrease. Their findings, published in Physical Review Letters and selected as an Editor’s Suggestion, introduce an entropy measure that is more closely connected to a black hole’s spin and energy. The researchers say this could improve scientists’ understanding of dynamic events such as black hole mergers and evaporation.

Why Hawking’s Framework Needed an Update

“The laws of black hole mechanics came directly from Einstein’s equations,” said Daniel E. Paraizo, a graduate student in physics at Penn State and an author of the paper. “Because you cannot see into a black hole, it seemed that there could be an infinite number of ways to make a black hole making their entropy infinite as well. They were also thought to only absorb energy and never radiate, so their temperature was zero.”

At first, those ideas made black holes appear incompatible with the familiar laws of thermodynamics because they seemed to have infinite entropy and no temperature. Hawking later changed that picture by using quantum mechanics to demonstrate that black holes can emit particles and energy.

“This changed the thinking about the thermodynamic properties black holes from a sort of mathematical concept described by equations, to being more of a physical reality,” Paraizo said. “This opened the door to finding analogies in black holes of entropy and temperature used in thermodynamics.”

Hawking proposed that the size of a black hole’s event horizon, the boundary beyond which even light cannot escape, is proportional to its entropy. He also showed that a black hole’s temperature depends on a combination of its mass and spin.

A Better Measure for Dynamic Black Holes

According to the researchers, the problem is that Hawking’s approach works only when a black hole is in equilibrium.

“There is a problem, though,” said Jonathan Shu, a graduate student in physics at Penn State and an author of the paper. “These analogies only really work for a black hole that is at equilibrium. In dynamic situations, event horizons can form and grow in what we call flat regions of space-time, where nothing is happening. This makes them teleological — their properties cannot be determined just by the local physics of the black hole but instead rely on prediction of events that may or may not happen in the future. Therefore, the area of event horizons cannot be a measure of the physical entropy of dynamical black holes. If we want to understand black holes that are growing, evaporating, and merging, we need a viable alternative.”

The team’s solution replaces the traditional event horizon with what physicists call a “dynamical horizon,” a concept that is already widely used in computer simulations of black holes. Unlike an event horizon, a dynamical horizon is defined by the black hole’s properties at a specific moment in time, avoiding the complications created by relying on future events.

“This allows us to extend the first and second laws of thermodynamics to black holes that are not at equilibrium, thereby overcoming the limitations of the paradigm that has been used for over half a century,” Ashtekar said. “We can apply these generalized laws to better understand evaporating black holes in quantum theory and black hole mergers, like those detected by the LIGO-Virgo-KAGRA collaboration using gravitational waves.”

The research was supported by the Penn State Atherton Professorship Program and the Penn State Eberly College of Science.

The theory accurately describes a wide range of microscopic phenomena. These include the famous double slit experiment, in which particles also display wave like behavior, and quantum tunneling, where particles have a probability of passing through a barrier even when they do not have enough energy to overcome it in the classical sense. Other key quantum effects, such as entanglement and coherence, now form the foundation of emerging technologies including quantum computing and quantum communication.

Are Complex Numbers Really Essential?

For decades, quantum mechanics has relied on complex numbers, which combine a real component with an imaginary component. In the mathematical description of a quantum state, the real part represents the amplitude, while the imaginary part represents the phase. This framework has long been considered essential for describing many quantum processes.

Even so, physicists have continued to debate whether complex numbers are truly a fundamental part of nature or simply a convenient mathematical tool. That question naturally leads to another: Could quantum mechanics be formulated using only real numbers?

Revisiting a Key Quantum Assumption

A 2021 study concluded that complex numbers are indispensable under the standard postulates of quantum mechanics (Renou et al., Nature 600, 625 (2021)). Experimental results also supported that conclusion.

Researchers from Heinrich Heine University Düsseldorf (HHU) and the German Aerospace Center (DLR), led by Professor Dr Dagmar Bruß and doctoral researcher Pedro Barrios Hita, decided to take another look at the assumptions behind that earlier work.

In a new study published in Physical Review Letters, they found that one of the postulates used in the 2021 analysis was more restrictive than necessary. By replacing it with a different, physically motivated approach for describing how quantum systems combine, they identified a family of theories that can be expressed entirely with real numbers while remaining experimentally indistinguishable from conventional quantum mechanics.

Professor Bruß said: “This means that both frameworks yield identical predictions for any conceivable experiment. Within this framework, imaginary numbers are thus not fundamentally necessary in quantum mechanics and can in principle be replaced by alternative formulations using real numbers.”