For years, scientists have known that regular physical activity can help lower the risk of dementia. But new USC research suggests that it’s not only the amount but also the activity’s context — for work or for leisure — that makes a difference.

A meta-analysis of more than 4.2 million people has found that leisure-time exercise — activities such as walking, cycling, running, swimming or playing sports — is associated with a substantially lower risk of dementia. In contrast, physical activity performed as part of a job appears to be linked with a higher risk of developing the condition.

Paradoxical results

The findings, published in The Lancet Public Health, are the first to systematically examine whether the so-called “physical activity paradox” extends to dementia. This paradox, well documented in cardiovascular research, describes the surprising observation that physically demanding jobs do not provide the same health benefits as voluntary exercise — and may even increase disease risk.

The research team, led by Professor of Biological Sciences and Anthropology David Raichlen of the USC Dornsife College of Letters, Arts and Sciences, analyzed data from 74 cohort and case-control studies involving more than 4.2 million participants aged 45 to 93 years across 30 countries. Participants were followed for a median of 10 years, during which investigators tracked diagnoses of all-cause dementia, Alzheimer’s disease and vascular dementia.

Overall, people who engaged in higher levels of leisure-time physical activity had a 24% lower risk of dementia than those who were least active. Household physical activity also appeared beneficial, although evidence came from only a single study. By contrast, occupational physical activity was associated with a 20% higher dementia risk, while active commuting showed a modest increase in risk, though those findings were based on just two studies.

“The findings challenge the long-held assumption that ‘every move counts’ for brain health,” said Natan Feter, the study’s first author, postdoctoral fellow in Raichlen’s Evolutionary Biology of Physical Activity Lab at USC and researcher in the Graduate Program of Epidemiology at Universidade Federal do Rio Grande do Sul in Brazil.

Work versus play

“Physical activity” often combines exercise, manual labor, housework and commuting into a single measure. But according to the researchers, these different forms of activity occur under very different circumstances and may have distinct effects on long-term health.

Leisure-time exercise is typically self-directed, can be performed at an enjoyable intensity and is often accompanied by social interaction or stress reduction. Physically demanding jobs, on the other hand, may involve repetitive tasks, prolonged standing, heavy lifting, limited recovery time and exposure to workplace hazards.

The authors argue that the apparent harms associated with occupational activity are unlikely to be caused by movement itself. Instead, they may reflect the broader social and environmental conditions that often accompany physically demanding work.

Manual occupations are more likely to involve psychosocial stress, less job control, hazardous working conditions and greater exposure to air and noise pollution — all factors that have independently been linked to dementia risk. Workers in these jobs may also have fewer opportunities for recreational exercise because of time constraints, fatigue or limited access to safe places for physical activity.

Leisure-time exercise and occupational physical activity exhibited contrasting nonlinear associations with dementia risk. Higher levels of leisure-time exercise were associated with progressively lower dementia risk until the association plateaued, while higher levels of occupational physical activity were associated with progressively greater dementia risk before also plateauing.

Further investigation ahead

The authors note that evidence remains sparse for household and commuting activity, preventing firm conclusions about those domains. Likewise, most of the available research came from high-income countries, even though low- and middle-income countries are expected to experience the largest increases in dementia cases over coming decades.

Another limitation is that nearly all included studies relied on self-reported physical activity, which can introduce recall bias. Still, the consistency of the results across multiple sensitivity analyses gives confidence that the association should be taken seriously, Feter said.

Researchers caution that the results do not mean people should avoid physically active jobs. Because the analysis is based on observational studies, it cannot prove that occupational activity causes dementia. Instead, the findings highlight the importance of considering the context in which physical activity occurs. Leisure-time activity remained protective, while occupational activity remained associated with elevated dementia risk even after accounting for age, education and chronic diseases.

Additionally, research that Raichlen, Feter and colleagues published last month in the journal Alzheimer’s & Dementia indicates that the context of sedentary behavior may have an impact on brain structures. In that study, physically sedentary but mentally active behavior, such as working while seated at a desk, was associated with higher volume in regions of the brain’s cortex, including areas responsible for executive function, when compared to passive sedentary activity such as watching TV.

The findings indicate the importance of activity context and carry implications for public health, the authors emphasized. Rather than simply encouraging people to “move more,” dementia prevention efforts should recognize that not all physical activity occurs under the same conditions.

“In other words, when it comes to protecting the brain, the context of physical activity may matter just as much as movement itself,” Raichlen said. “Improving access to safe parks, walking trails and recreational facilities, ensuring people have adequate leisure time for exercise, and reducing harmful workplace exposures may ultimately prove as important as promoting physical activity itself.”

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About the study: Raichlen and Feter’s co-authors include Tiladia Markarian, Dylan M. Luong, Jack Gunnink, Anamika Nanda, Sarah Hourihan and Ashley Ventura of USC; Eduardo Caputo, Jayne Feter, Gustavo S. Silva and Airton José Rombaldi of Universidade Federal de Pelotas, Brazil; Paula Iso-Markku of the University of Helsinki; Daniela Benzano Bumaguin of Fundação Universitária de Cardiologia, Brazil; Yann C. Klimentidis and Gene E. Alexander of the University of Arizona; Daniel Umpierre and Natália Schröder of Universidade Federal do Rio Grande do Sul, Brazil; and Pedro C. Hallal of University of Illinois Urbana-Champaign.

This research was supported by grants P30AG072980, P30AG019610, R56AG067200, R01AG064587 and R01AG072445 from the National Institutes of Health and funding from the state of Arizona, the Arizona Department of Health Services and the McKnight Brain Research Foundation. This study was also financed in part by the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) (25/2551-0002834-5) and the National Council for Scientific and Technological Development – CNPq and Department of Science and Technology of Secretariat of Science, Technology, Innovation and Health Complex of Ministry of Health of Brazil – MoH (445538/2023-6).

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What do “epigenetic clocks” actually measure? These lab tests have become popular tools for studying biological aging, or how the body’s cellular function changes at a faster or slower rate than expected. However, the underlying biology behind each of these measurements has remained largely unknown until now.

A recent USC Leonard Davis School of Gerontology-led study published in npj Aging shows the variability in what five of the most widely used epigenetic clocks are actually measuring. The research team also developed new gene-expression based clocks to complement existing epigenetic clocks, which show even stronger predictive power for age-related disease and mortality.

Biology versus the calendar

Scientists have long known that people age at different rates biologically. Someone who is 70 years old on paper may have the health of a much younger person, while another 70-year-old may be much more frail than their same-age peers.

To measure that difference, researchers use epigenetic clocks to estimate biological age. These tools measure a chemical change called DNA methylation, which doesn’t change the genetic code itself but affects which genes are turned “off” or “on.” These chemical changes on top of the base DNA are collectively called the epigenome.

Examining the epigenome can predict health problems and even the risk of death better than chronological age alone. But until now, scientists did not know exactly what was happening inside cells that made the epigenetic clocks such powerful tools.

“Aging isn’t just about the number of candles on your birthday cake — it’s also about what’s happening inside your cells,” said lead author T. Em Arpawong, research associate professor of gerontology at the USC Leonard Davis School. “We found that different clocks capture different aspects of the biology of aging and developed new transcriptomic aging gene scores that complement existing clocks and, in some cases, better predict age-related disease and mortality.”

Surprising differences

In the study, Arpawong and the team studied blood samples from 3,227 participants in the Health and Retirement Study in the U.S. They compared DNA methylation patterns with gene expression, or how often genes are transcribed from DNA into RNA and used to make proteins. All of the transcription taking place within a cell at a given time is referred to as the transcriptome.

The researchers examined combined epigenetic and transcriptomic measurements to compare gene expression and identify the biological pathways highlighted by each of five epigenetic clocks.

They found that each aging clock was associated with different biological processes, from energy balance and cellular growth to immune cell activation and inflammatory signaling. Even though the clocks emphasized different biological pathways, they shared several common themes, including changes in the immune system, metabolism and cell communication — all well-known features of aging.

A new tool for prediction

The researchers further used the analysis to create new tools called transcriptomic aging gene scores (TAGS). The combined approach provided an even clearer picture of a person’s biological health; in several cases, TAGS predicted health outcomes such as frailty, walking speed, heart disease, diabetes, lung disease and death better than the epigenetic clocks alone.

The findings could help researchers choose the best aging clock for different studies. For example, one clock may be better for studying treatments that target the immune system, while another may be better for testing therapies that improve metabolism or slow the decline in physiological resilience.

The work also helps explain the biology behind tools that are becoming increasingly common in aging research. By linking DNA methylation changes with gene expression activity, senior author Eileen Crimmins said the study has further illuminated the “black box” of biological aging clocks, bringing scientists one step closer to using these measures to better predict disease, track healthy aging and one day guide medical care.

“By uncovering the molecular programs behind these biomarkers, our findings improve their interpretability and help guide their use in geroscience, epidemiology, and future clinical applications,” she said.

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About the study: Arpawong and Crimmins’ co-authors included Harshanna Badhesha, Jung Ki Kim, Christopher Beam, Kimberly Siegmund of USC; Steve Cole of UCLA; Eric T. Klopack of Indiana University; and Bharat Thyagarajan of the University of Minnesota. The study was supported by the National Institute on Aging (P30 AG017265).

Once or twice a week, chronic pain researcher Jason Kutch rises at dawn and heads to a Los Angeles-area surf break to catch some waves.

Kutch studies the effect of surfing on brain activity — but during those early morning surf sessions, he’s completely focused on keeping his balance in the crashing water.

“You have to coexist with this extremely powerful force that demands all of your attention,” says Kutch, a professor in the USC Division of Biokinesiology and Physical Therapy.

Kutch and Peter Westwick, professor of the practice of thematic option and history at the USC Dornsife College of Letters, Arts and Sciences, are both experts in the science and technology of surfing. Kutch is studying whether surfing can positively shift brain activity and relieve chronic pain. Westwick, also a surfer, explored the tension between the sport’s natural and engineered elements as co-author of The World in the Curl: An Unconventional History of Surfing.

Yet both scholars believe that waves’ appeal and healing potential can’t be fully captured by data. Their experiences as surfers inform their insights into how this elemental force of nature shapes culture and health.

Communion with nature

In ancient Hawaii, where surfing emerged perhaps 1,500 years ago, the activity was woven into every aspect of cultural life, from courtship rituals to religious festivals, Westwick says.

The Hawaiian language reflects a belief in riding waves as a philosophical pursuit. “Nalu, the Hawaiian word for surf, can also mean to search for truth,” he says. “Additionally, nalu refers to the amniotic fluid that covers babies. Hawaiians were born surfing.”

Waves connect us not just to the watery environment of our mother’s wombs, but to Mother Nature — even as surfboards, wetsuits and even some features of the coastline are products of human engineering.

“Part of the attraction for surfers is that we are literally immersed in the natural world,” says Westwick, who surfs near his home in Santa Barbara. “We sit on our boards looking out to sea with our backs literally and figuratively turned on modern industrial civilization.”

‘Riding nature’s energy bands’

Though the marine environment offers a soothing counterpoint to the stresses of modern life, waves are unpredictable and, at times, destructive.

“Most ocean waves are a conversion of the wind energy of very distant storms,” Westwick says. “These disturbances on the ocean surface can travel thousands of miles and eventually reach a coastline. Close to shore, the ocean gets shallower, causing the waves to rise up, topple over and break.”

Surfing offers a direct experience of these powerful and capricious forces.

“If you catch a wave on your surfboard, this energy of distant storms has now been transferred to you,” he says. “You’re riding nature’s energy bands.”

Flight and flow

For Kutch, that energy transfer provides a singular thrill. “There’s something about shooting down that unbroken wave while standing on the board, and it can’t be described by any other term than ‘flying,’” he says.

Kutch notes that staying afloat is a delicate balancing act, both physically and mentally.

“Surfing is a repeated, goal-directed task in a highly sensory-rich environment that fluctuates moment to moment,” Kutch says. “That engages mechanisms in the brain in a special way.”

Kutch has identified a marker of brain activity called peak alpha frequency that may shift favorably after a surfing session and could be a factor in chronic pain relief. This scientific phenomenon highlights a poetic symmetry: ocean waves influence our brain waves.

Grappling with the ocean’s flow can also encourage a mental state known as “flow”: deep focus and total absorption in an activity. Artists, athletes and others have described flow as akin to being carried along by a water current.

In surfing, the concept is both literal and metaphoric: “A flow state can positively redirect your attention away from pain, anxiety and depression,” says Kutch, who credits surfing with resolving his own chronic pain. “I think there’s some magic in that space.”

 

Some of medicine’s smallest patients can present its biggest imaging challenges. An infant’s heart can be as small as a walnut, beating rapidly inside a body that will change dramatically as the child grows. Yet much of the equipment used in MRI comes in standard sizes better suited to adult bodies, and customized versions can cost thousands of dollars and take months or even years to manufacture.

USC researchers have developed a potential solution: flexible MRI sensors that can be customized to individual patients and 3D-printed in less than 10 minutes for about $30. In testing, the sensors produced roughly four times greater image contrast than standard commercial versions.

“By making customized MRI equipment faster and more affordable to produce, we have the potential to bring better imaging to patients who have traditionally had fewer options, especially infants and children,” said Yasser Khan, assistant professor of electrical and computer engineering and biomedical engineering at the USC Viterbi School of Engineering, whose lab at the USC Michelson Center for Convergent Bioscience designs and 3D-prints the customized coils.

Paired with specialized MRI technology at the USC Michelson Center, the sensors can also help capture anatomy in motion, including something as small and fast-moving as a beating heart.

“We’re bringing a level of precision and customization to MRI that isn’t available today,” he said.

A better fit for growing bodies

MRIs use powerful magnets and radio waves to generate signals from inside the body, which a computer then turns into detailed images. Devices called coils act like antennas to pick up those signals, and the closer they fit to the area being scanned, the clearer the image can be.

That makes fit especially important for small patients. A coil designed for an adult may leave gaps when placed around an infant or child, making it harder to capture a strong signal. And because children grow rapidly, equipment that fits at one stage may not fit as well a few years or even months later.

Khan compares the challenge to choosing the right camera lens.

“If you use a large lens to image something very small, you’re not going to get the clearest picture,” Khan said. “But if you can tailor the lens, in this case the MRI coil, to the individual patient, you can capture a much better image.”

The researchers wanted to make a coil that could closely follow the contours of the body rather than leave space between the sensor and the skin. That required rethinking both the material and the way MRI coils are manufactured.

After about three years of experimentation, Khan’s team developed a process for 3D printing conductive silver ink onto a thermoplastic elastomer, a soft, stretchable material with properties similar to human skin. The material can stretch roughly 5% to 10%, allowing the coil to bend and move with the body.

The team tested different flexible materials, plastics and formulations of printable metal before arriving at the combination of silver ink and thermoplastic elastomer. The researchers also had to develop the electronics needed to connect the unconventional coils to an MRI system.

Because the coils begin as digital designs, their dimensions can be changed quickly. A researcher can adjust the size or shape on a computer and print a new coil rather than wait for a specialized part to be manufactured.

“For a growing child, that could mean creating different coils as the body changes,” Khan said. “The goal is to give children access to imaging equipment designed for their bodies, so doctors can get the clearest picture possible as they grow.”

Built and tested under one roof

The technology grew out of the kind of interdisciplinary collaboration the USC Michelson Center was designed to foster, bringing engineers, imaging scientists and clinicians together to tackle complex challenges and accelerate scientific discovery.

In this case, two labs brought complementary expertise to the same problem. 

The Khan Lab specializes in flexible and wearable electronics, including devices that can bend, stretch and conform to the body. 

The Dynamic Imaging Science Center (DISC), led by Krishna Shrinivas Nayak, professor of electrical and computer engineering and biomedical engineering at USC Viterbi, develops advanced MRI technologies, including methods for capturing the body as it moves.

The DISC Lab is also home to what researchers describe as the only MRI system of its kind in the world, allowing USC scientists to test new technologies and push the boundaries of imaging the body in motion.

Clinical collaborators help connect those capabilities to the needs of patients. John Wood, director of cardiovascular MRI at Children’s Hospital Los Angeles and professor of pediatrics and radiology at the Keck School of Medicine of USC, works with Nayak on some of the most difficult challenges in pediatric imaging, including real-time imaging of the fetal heart. His experience imaging children’s hearts helps inform where new, more adaptable technologies could have the greatest impact.

“We need environments where different ideas can collide,” Khan said. “This project wouldn’t have happened without access to the MRI and conversations with cardiologists, radiologists and imaging scientists. When you bring that expertise together, you can solve problems none of us could solve alone.”