Recent studies from the USC Leonard Davis School of Gerontology highlight how environmental and social factors, such as heat exposure and education, play a major role in shaping biological aging. At the same time, new advances in measuring biological age, including the development of a novel tool known as Physiological health Age (PhysAge), are giving scientists better ways to understand these effects.
Biological aging refers to how the body is changing over time, including how well organs and systems are working. For example, two people who are both 65 may look very different inside: One may have the biological profile of someone younger, while another may show signs of aging earlier.

“Biological age gives us a clearer picture of health than chronological age. It helps us understand who is likely to stay healthy longer and who may be at higher risk for disease and disability,” says USC University Professor Eileen Crimmins.

Crimmins is a pioneer in the field of biodemography, or the linking of biological measurements to large amounts of population data. Recent research led by Crimmins, her USC Leonard Davis School colleagues and their trainees has shed light on how social factors may be more deeply entwined with human biology and health outcomes than previously thought.

Heat Exposure May Accelerate Aging

A February 2025 study led by USC researchers found that extreme heat may speed up the biological aging process for older adults. The study examined data from more than 3,600 participants in the national Health and Retirement Study. Blood samples taken at various time points during a six-year period were analyzed for epigenetic changes, or changes in the way individual genes are turned “off” or “on” by a process called DNA methylation.

Researchers discovered that older adults living in U.S. counties with more days of extreme heat had higher biological ages than peers of the same chronological age in cooler areas. This correlation persisted even after controlling for socioeconomic and other demographic differences, as well as lifestyle factors such as physical activity, alcohol consumption and smoking, says first author Eunyoung Choi, a USC Leonard Davis PhD in Gerontology alumna and postdoctoral scholar.

Choi notes that participants living in high-heat areas like Phoenix, where “Extreme Caution” heat days (with temperatures of 90 degrees or above) occur half the year, experienced up to 14 months of additional biological aging compared with those living in areas with fewer than 10 heat days per year.

“Even after controlling for several factors, we found this association,” she says. “Just because you live in an area with more heat days, you’re aging faster biologically.”

The study adds to evidence that climate change could have long-term health consequences beyond immediate risks such as heatstroke. The next steps for the researchers will be to determine what other factors might make someone more vulnerable to heat-related biological aging and how it might connect to clinical outcomes.

In the meantime, the study results could also prompt policymakers, architects and others to keep heat mitigation and age-friendly features in mind as they update cities’ infrastructure, from placing sidewalks and bus stops in shaded areas to planting more trees and increasing urban green space, says Jennifer Ailshire, senior author of the study and professor of gerontology and sociology at the USC Leonard Davis School.

“If everywhere is getting warmer and the population is aging, and these people are vulnerable, then we need to get a lot smarter about these mitigation strategies,” Ailshire says.

Education Linked to Slower Biological Aging

Another USC-led study, published in August 2025, showed that higher levels of education are associated with slower biological aging. Using data from the U.S. Health and Retirement Study, researchers examined how years of schooling were related to DNA methylation-based measures of biological age.

They found that individuals with more education tended to have lower biological ages than peers with less education, even when they were the same chronological age. Importantly, the relationship held even after accounting for differences in income, suggesting that education and its associated life circumstances have a lasting impact on health.

“Education shapes opportunities and risks throughout life,” says Crimmins, who authored the study with former USC Leonard Davis postdoctoral researcher Mateo Farina, now an assistant professor at the University of Texas at Austin, and Jung Ki Kim, a USC Leonard Davis research associate professor. “It’s a powerful social determinant of health, and it is leaving a mark on how fast or slow our bodies age.”
This finding highlights how social and behavioral factors leave marks that can be detected in the biology of aging. Access to education not only affects career and economic outcomes but also appears to extend into the cellular processes that determine longevity and healthspan.

A New Tool to Measure Biological Aging

Understanding the links between environmental exposures and biological aging requires complex tools. A September 2025 study led by USC Leonard Davis Research Associate Professor Thalida Em Arpawong and colleagues introduces one such tool: Physiological health Age (PhysAge).

PhysAge is a DNA methylation–based measure that combines information from eight biological systems, including immune, cardiovascular, respiratory, renal, metabolic and endocrine functions. Unlike earlier epigenetic clocks, which were trained primarily on mortality data, PhysAge was designed around established clinical biomarkers such as glycated hemoglobin, cholesterol, inflammation and lung function.

In testing, PhysAge was as effective as or better than widely used epigenetic clocks like GrimAge and DunedinPACE in predicting frailty, disability, cognitive decline and mortality. Because it reflects specific systems, it can also indicate which areas of health are most affected.
“Our goal was to create an interpretable clock that not only represents the overall physiological health state but also provides insight into which of its constituent systems may be driving accelerated aging,” Arpawong says. “PhysAge allows us to connect environmental and behavioral exposures to the specific biological systems and inform us about which ones may be at greater risk and require closer clinical monitoring and earlier intervention.”

Together, these studies illustrate how biological aging is shaped by more than just genetics or the passage of time. Environmental stressors such as heat exposure and social factors such as education leave measurable effects on the body’s molecular aging processes.
Tools like PhysAge make it possible to detect these effects and provide more information on health impact. For example, heat stress may accelerate cardiovascular and kidney aging, while education may help preserve metabolic or immune health. By identifying these physiological pathways, researchers can better understand why certain groups are more vulnerable and how interventions might slow biological decline.

Implications for Public Health

The ability to measure biological aging has practical implications for both health care and policy.

If heat exposure is shown to consistently accelerate biological aging, then urban planning measures to address heat risks could become recognized as interventions that not only improve comfort but also protect long-term health, Ailshire notes.

Similarly, education policy can be understood as health policy. Investments in early and lifelong education may contribute to healthier aging across the population. With measures like PhysAge, researchers and policymakers could eventually quantify the benefits in terms of years of biological life preserved.

As climate change accelerates and populations age, the intersection of environment, inequality and biology will become an increasingly urgent area of study. The hope is that with better measurement tools and clearer understanding of risk factors, scientists, clinicians and policymakers can take steps not only to extend lifespan but also to improve healthspan — the years of life lived in good health.

“We’re experiencing increased life expectancy, but this additional time is largely time spent living with disease,” Crimmins says. “To increase healthspan, we have to intervene much earlier in the process of health change. Knowing more about how social factors interact with biology can tell us how to best intervene.”

The post More Than Just Genes: Many Factors Affect How Fast We Age appeared first on USC Leonard Davis School of Gerontology.

“This link between biological age and extreme heat remained even after accounting for a wide range of individual and community factors such as physical activity levels and socioeconomic status. This means that even among people with similar lifestyles, those living in hotter environments may still be aging faster at the biological level,” Choi wrote. “Even more surprising was the magnitude of the effect – extreme heat has a comparable impact on speeding up aging as smoking and heavy alcohol consumption. This suggests that heat exposure may be silently accelerating aging, at a level on par with other major known environmental and lifestyle stressors.”

The post Column: Extreme heat silently accelerates aging on a molecular level − new research (The Conversation) appeared first on USC Leonard Davis School of Gerontology.

People in neighborhoods that experience more days of high heat show greater biological aging on average than residents of cooler regions, said Jennifer Ailshire, senior author of the study and professor of gerontology and sociology at the USC Leonard Davis School.

Biological age is a measure of how well the body functions at the molecular, cellular, and system levels, as opposed to chronological age based on one’s birthdate; having a biological age greater than one’s chronological age is associated with higher risk for disease and mortality. While exposure to extreme heat has itself long been associated with negative health outcomes, including increased risk of death, heat’s link to biological aging has been unclear.

Measuring epigenetic changes

Ailshire and her coauthor Eunyoung Choi, USC Leonard Davis PhD in Gerontology alumna and postdoctoral scholar, examined how biological age changed in more than 3,600 Health and Retirement Study (HRS) participants aged 56 and older from throughout the U.S. Blood samples taken at various time points during the six-year study period were analyzed for epigenetic changes, or changes in the way individual genes are turned “off” or “on” by a process called DNA methylation.

The researchers used mathematical tools called epigenetic clocks to analyze methylation patterns and estimate biological ages at each time point. They then compared participants’ changes in biological age to their location’s heat index history and number of heat days reported by the National Weather Service from 2010 to 2016.

The National Weather Service Heat Index Chart categorizes heat index values into three levels based on the potential risk of adverse health effects. The “Caution” level includes heat index values ranging from 80°F to 90°F, the “Extreme Caution” level includes values between 90°F and 103°F, and the “Danger” level includes values between 103°F and 124°F. Days in all three levels were included as heat days in the study.

The analysis revealed a significant correlation between neighborhoods with more days of extreme heat and individuals experiencing greater increases in biological age, Choi said. This correlation persisted even after controlling for socioeconomic and other demographic differences, as well as lifestyle factors such as physical activity, alcohol consumption and smoking, she added.

“Participants living in areas where heat days, as defined as Extreme Caution or higher levels (≥90°F), occur half the year, such as Phoenix, Arizona, experienced up to 14 months of additional biological aging compared to those living in areas with fewer than 10 heat days per year,” she said. “Even after controlling for several factors, we found this association. Just because you live in an area with more heat days, you’re aging faster biologically.”

All three epigenetic clocks employed in the study – PCPhenoAge, PCGrimAge, and DunedinPACE – revealed this association when analyzing epigenetic aging over a 1- to 6-year period. PCPhenoAge also showed the association after short (7 days) and medium (30-60 days) periods of time, indicating that heat-related epigenetic changes could happen relatively quickly, and some of them may accumulate over time.

Climate implications for communities

Older adults are particularly vulnerable to the effects of high heat, Ailshire said. She noted that the study used heat index, rather than just air temperature, to take relative humidity into account as they analyzed results.

“It’s really about the combination of heat and humidity, particularly for older adults, because older adults don’t sweat the same way. We start to lose our ability to have the skin-cooling effect that comes from that evaporation of sweat,” she explained. “If you’re in a high humidity place, you don’t get as much of that cooling effect. You have to look at your area’s temperature and your humidity to really understand what your risk might be.”

The next steps for the researchers will be to determine what other factors might make someone more vulnerable to heat-related biological aging and how it might connect to clinical outcomes. In the meantime, the study results could also prompt policymakers, architects, and others to keep heat mitigation and age-friendly features in mind as they update cities’ infrastructure, from placing sidewalks and building bus stops with shade in mind to planting more trees and increasing urban green space, Ailshire said.

“If everywhere is getting warmer and the population is aging, and these people are vulnerable, then we need to get really a lot smarter about these mitigation strategies,” she said.

—

The study, “Ambient Outdoor Heat and Accelerated Epigenetic Aging among Older Adults in the U.S.,” appeared in the journal Science Advances on February 26, 2025. Funding for the study included the USC/UCLA Center on Biodemography and Population Health through a grant from the National Institute on Aging, National Institutes of Health (P30AG017265) and The Network on Life Course Health Dynamics and Disparities in 21st Century America funded by the National Institute on Aging, National Institutes of Health (R24AG045061).

The post Study: Extreme Heat May Speed Up Aging in Older Adults appeared first on USC Leonard Davis School of Gerontology.

About 35 miles south in Fullerton, Jiu-Chiuan Chen prepares for his daily run through his tree-lined neighborhood. When the USC physician and epidemiologist steps outside, he spots a gray-brown haze hugging the horizon. He checks the Air Quality Index on his phone and goes back inside.

In Culver City, Lauren Salminen considers the wisdom of hiking in the Santa Monica Mountains. She can see a misty scrim in the distance, but is that morning fog or smog? The USC neurology instructor decides this might be a day for yoga indoors.

These USC scientists—each an experienced researcher in brain aging—know that air pollution does more than ruin a good workout. Medical science has long recognized the impact of air pollution on the lungs, but now research at USC is helping define the environment’s impact on the brain. Growing evidence links the long-term effects of dirty air to accelerated cognitive decline and dementia.

USC researchers, including Chen, hope to better understand environmental effects and gene-environment interactions on brain health. “USC has the perfect soil to grow this new area of research,” he says.

An Inspiration Point

The USC Children’s Health Study, launched in 1993 and now involving about 12,000 school-age children, is one of the nation’s largest and longest-running research projects on children’s respiratory health. Its researchers have contributed crucial data that have deepened understanding of lung health, including evidence that kids who live in more polluted areas have poorer lung function, reduced lung growth, and more asthma and lung damage than those in less-polluted areas.

When kids move away from polluted neighborhoods, their lung function improves, a discovery that has inspired other scientists to ask: If L.A.’s bad air is affecting our breathing, what about our brains?

What they’re finding is critical, including who is most at risk. “The aging brain is vulnerable to air pollution,” says Caleb Finch, a USC University Professor, gerontologist and expert on the biology of aging and also co-principal investigator in the AirPollBrain Group. “For too long, the role of environmental neurotoxins in Alzheimer’s disease has been neglected.”

Within a few years of joining forces, Chen and Finch reported the first evidence that a critical Alzheimer’s risk gene—APOE4—speeds brain aging when it interacts with fine air particles.

In 2011, the colleagues received the first-ever National Institutes of Health grant to study the connections between air pollution and Alzheimer’s. Since then, about one-fourth of the 220 NIH-funded research grants focused on air pollution and dementia have come to USC.

Finch and Chen have also succeeded in attracting more than two dozen USC scientists to the AirPollBrain Group, crossing disciplines and schools to unite neuroscientists, environmental health experts, engineers, gerontologists, physicians, sociologists and more. The result: In 2018, the National Institute on Aging awarded USC researchers a five-year $11.5 million grant to examine how urban air pollution contributes to an increased risk of dementia.

Small Particles Make a Big Impact

Air pollution wreaks havoc primarily through systemic inflammation, Finch says, and that exposure can lead to the formation of amyloid plaques, the proteins that form between the brain’s nerve cells that are the hallmarks of Alzheimer’s.

Researchers have fine particle pollution, also known as PM2.5, in their sights. The tiny, inhalable pollutants come from cars, power plants and coal and wood-burning fuel. Its name comes from its size—smaller than 2.5 microns in diameter or about 30 times smaller than the width of a human hair. But the impact, once inhaled, is huge.

The microscopic particles can pass directly through the nose into our lungs and may even slip through the blood-brain barrier, which is supposed to protect our brains from all invaders. “Pollution is breaking down our barriers,” says Megan Herting, a USC public health scientist whose lab uses advanced neuroimaging to study how the brain develops during childhood.

For reasons not yet fully understood, women in their 70s and 80s who live in areas with high levels of air pollution are at particular risk for Alzheimer’s-like brain shrinkage compared with women who routinely breathe cleaner air.

But kids aren’t immune. USC studies have shown that even at relatively low levels, toxic air may alter the size of a child’s developing brain and boost the risk of cognitive and emotional problems in adolescence.

How Bad is Our Air?

The Los Angeles-Long Beach region ranks first in the nation for ozone pollution and fourth in year-round fine particle pollution, according to the American Lung Association.

Pollution declines in the last 10 to 15 years nationally and in L.A. have been a public health success story. “It shows that if we put our minds to it, we can make our environment a healthier place to live,” Ailshire says. In 2021, she and Finch, her colleague in the USC Leonard Davis School of Gerontology, reported in separate studies that showed a decrease in neurotoxic PM2.5 air pollution in humans and in laboratory studies.

In the last few years, she has seen some backsliding to unhealthy levels. “We have to be constantly vigilant,” she says. “We can’t get ahead of ourselves and declare a victory.”

Ailshire is particularly interested in the “social ecology” of air pollution—the intersection of socioeconomic and physical risks—driven by the fact that polluted air tends to be worse in poorer neighborhoods. “Air pollution isn’t just a physical characteristic,” Ailshire says. “It’s a social phenomenon produced by humans, for the most part.”

Finch has been studying brain health for decades. In experimental studies, he and his team have shown that air pollution damages some parts of the brain that also are vulnerable to Alzheimer’s disease. Multiple factors influence the odds someone will develop Alzheimer’s disease. “There’s no silver bullet—it’s a machine gun,” Finch says. An individual’s risk can be a combination of several things, and air and chemical pollution are high on that list.

Tracking Pollution’s Impact Across the Lifespan

Within the Southern California Environmental Health Sciences Center at USC, program leaders Chen and Herting work at opposite ends of the age spectrum to pinpoint the environmental determinants of cognitive decline. Increasingly, evidence shows that older people are more likely to develop dementia if they live in places that have high PM2.5. Chen’s research has shown that women in their 70s and 80s are particularly vulnerable to structural changes in the brain and memory loss, for reasons not yet fully understood.

Chen also has found that PM2.5 particles are tied to the disproportionate number of Black Americans affected by dementia, partly because people of color are statistically more likely to live in neighborhoods near polluting facilities. Even when researchers accounted for the incidence of cardiovascular disease and other factors, Black women were twice as susceptible as non-Hispanic whites to dementia risk from air pollution. “That is a puzzle we still have to solve,” Chen says.

Air pollution also can affect children’s brain development. “One of the young brain’s most important jobs is creating efficient pathways,” Herting says. These pathways are critical because they form the essential brain circuitry that supports future learning and life skills. Lately, she’s focusing on kids 9 to 10, ages at which, she says, brain cells proliferate and prune themselves as kids head into adolescence. Herting’s team has demonstrated that kids exposed to noxious air have smaller areas in their brains associated with cognitive function and larger areas associated with emotion than kids breathing less-polluted air.

Her work is part of the national Adolescent Brain Cognitive Development Study, the largest investigation of its kind in the U.S. “We’re adding the environmental factor, one of the least-investigated areas,” she says.

To understand the bigger picture across the lifespan, Chen and Herting collaborated with Salminen, instructor of research neurology at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, to create the ENIGMA-ENV Working Group. “We know things like air pollution can increase dementia risk and vascular problems decades after exposure,” Salminen says. “But we have so much to learn about the processes that underlie those changes.”

Together, they are pooling brain scans from more than 60,000 people worldwide, who span all ages and range from healthy to those diagnosed with neurological disorders. The scientists rely on geospatial technology to map each participant’s home location and pollution exposure.

This global study builds on the success of ENIGMA Consortium, an international medical network of neuroimaging researchers studying major diseases of the brain, led by USC Stevens Associate Director Paul M. Thompson. “The ENIGMA-ENV Working Group is a truly global quest to identify environmental factors that help or harm our brain,” says Thompson, one of USC’s leading Alzheimer’s researchers. “Comparing data worldwide should reveal what factors help our brains develop and age, and what protects us against mental illness, which may ultimately guide public health policy.”

With this big-picture effort, USC is reaching beyond its Los Angeles roots to examine air pollution across all ages and sources. “We’re excited to be able to get more specific about what we mean when we say ‘air pollution,’” Salminen says.

Protecting Ourselves Now and Beyond

What can we do to protect our brain health? Moving away from highly polluted areas may be the ultimate protective strategy, but that option isn’t open to everyone. So USC scientists are on the hunt for other defenses.

In a study published in August 2020, Chen and his fellow authors looked at the protective powers of eating fish loaded with omega-3 fatty acids. “We found that women with higher blood levels of omega-3s had larger volumes of white matter in their brains,” he says—even women living in locations with higher PM2.5 levels. White matter, most of the brain’s volume, represents a vast system of neural connections. Its loss is considered an early marker of Alzheimer’s disease.

Next, Chen and Finch plan to expand their search for pollution counterbalances into supplements such as vitamins B, C and E. But they expect that any potential formula will not be one-size-fits-all.

The data generated at USC could have lasting implications for clean air standards and other regulations. Chen would like to see laws restricting placement of assisted living facilities near freeways much as is done now with schools. Herting wants air pollution facts to empower people to make their own decisions, “including who they want to elect to represent them on this life-critical issue,” she says.

She moved to Los Angeles from Oregon, where she was an avid runner. She’s mostly given that up. Before the birth of her daughter in December 2021, she was studying the locations of day care centers and schools in relation to L.A.’s byways.

When Finch arrived at USC in 1972, the federal Environmental Protection Agency was just 2 years old, and L.A. was infamous for its thick, hazy air. For decades, air quality officials warned the public to stay indoors on high smog days. Finch searched the L.A. Basin for a place with cleaner skies, eventually landing in northern Pasadena.

He lives there still and considers that health decision as important as the ones made about diet and exercise. When he drives, he keeps his car vents closed. A little self-protection goes a long way, he says, “but you can’t walk around the city with a scuba tank filled with oxygen on your back.”

In many ways, he’s optimistic about the future, inspired by the energetic brain-health collaborations at the university. “I could not imagine,” he says, “being able to do this kind of multidisciplinary work anyplace outside USC.”

This story first appeared in the spring 2022 issue of Trojan Family Magazine. Illustrations by Jason Holley.

The post Your Brain on Air Pollution appeared first on USC Leonard Davis School of Gerontology.

Air pollution and the brain

In particular, research has shown that higher exposure to air pollution is strongly associated with cognitive impairment and Alzheimer’s disease, especially for people with certain genetic risk factors for the disease, says University Professor Caleb Finch.

Finch, who holds the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School, has studied air pollution’s effects on the brain for several years, especially the consequences of exposure to fine particulates found in pollution from automobiles, factories and more. Many studies show that poor air quality accelerated aging processes in many tissues, including arteries and brain, with a sizeable impact on cognitive health, he explains.

“As we work to understand the biology of Alzheimer’s disease and develop interventions for prevention and treatment, efforts to improve air quality will also be critical for reducing cognitive decline and Alzheimer’s,” Finch says.

Environmental effects aren’t equal

The impact of air pollution isn’t evenly distributed, adds Associate Professor Jennifer Ailshire. Recent research has shown how older adults are especially susceptible to the health problems associated with environmental pollution, she says: “Most of the research had been conducted in younger populations in children and adolescents and in younger adults, but just in the past 10 years, it’s become really clear that older adults are a vulnerable population and that they’re more likely to suffer adverse consequences from chronic exposure to air pollution, and also from these acute episodes.”

Assistant Professor Joseph Saenz, who has studied health and cognition in older adults living in rural and urban areas of Mexico, says environmental risks often disproportionately affect socioeconomically disadvantaged populations. Rural populations in Mexico often have higher levels of poverty, lower levels of education, and less access to healthcare; in addition, lack of infrastructure in rural settings can introduce other environmental risks.

“In urban areas, we know that people have high exposure to air pollution from the outdoor environment. In Mexico City, we see the smoggy skies and we see this high level of air pollution that people are breathing in urban areas,” Saenz explains in an episode of the Lessons in Lifespan Health podcast. “However, in rural areas in Mexico, a significant portion of the population relies on solid cooking fuels, such as wood and coal. When people use these solid fuels for cooking, particularly inside the house, you can imagine how quickly the pollution builds up inside the home. … And in my own work, looking at the effects of indoor air pollution from solid cooking fuels, I find that people who cook with these solid cooking fuels tend to have lower cognitive functioning and also more rapid cognitive decline.”

Healthier land, healthier people

Improving the quality of food and reducing the burden of malnutrition, which also more heavily affects people of lower socioeconomic status, starts at the environmental level, say USC Leonard Davis Master of Science in Nutrition, Healthspan and Longevity graduates Brooklin White MS ’21 and Amylee Amos MS ’17.

In an article for the Hunger and Environmental Nutrition practice group of the Academy of Nutrition and Dietetics, White and Amos discuss how the microbiome of the soil used in farming could affect the microbiome within the human gut. “Restorative agriculture” farming practices, which aim to increase soil health and biodiversity, could provide benefits for both environmental and human health, and registered dietitian nutritionists can play a role in helping their clients get higher-quality food from the ground up, they say.

“RDNs can help society understand the connection between the soil microbiome, food quality, and human and planetary health,” say White and Amos. “We can demonstrate ideas surrounding regenerative agriculture by encouraging practices such as gardening and composting through community and school gardens, backyards, or window ledges. … Various studies have shown that gardening combined with dietetic support can improve interest in cooking and consuming home-grown foods, improve biometric markers such as HbA1c, and reduce BMI levels.”

The post Healthy Planet, Healthy Aging appeared first on USC Leonard Davis School of Gerontology.

University Professor Caleb Finch

Higher exposure to air pollution is strongly associated with cognitive impairment and Alzheimer’s disease, especially for people with certain genetic risk factors for the disease. Exactly how pollution interacts with these genes to increase dementia risk is still unknown, but clues may be found in how stem cells within the brain undergo aging, according to USC researchers.

University Professor Caleb Finch is the principal investigator on a new project investigating how neural stem cells in mice age in regard to both air pollution exposure and mutations in the gene for amyloid precursor protein (APP). Michael Bonaguidi, assistant professor of stem cell biology and regenerative medicine, gerontology and biomedical engineering, is co-PI on the project. The new study is supported by a $500,000, two-year grant from the Cure Alzheimer’s Fund.

In normal aging, the brain’s stem cells multiply and proliferate less and less over time, but this decline in neural stem cell activity occurs more rapidly in Alzheimer’s disease. Pilot data for the new project indicate that mice who were exposed to air pollution also showed slower neural stem cell replication as well as increased amyloid beta protein, or Aß, which makes up the “plaques” of protein often seen in brains of Alzheimer’s patients.

Studying neural stem cells and analyzing their responses to air pollution on a single-cell basis could identify specific molecular pathways affected by pollution that lead to damage and decline as well as illuminate possible targets for treatments, Finch said. The project will also include an investigation of the effects of BPN-15606, an anti-amyloid drug developed by the Cure Alzheimer’s Fund, which appeared to protect mice against neural stem cell loss during air pollution exposure in a pilot study.

“These studies are the first to examine neural stem cell aging at the single-cell level for modulation by air pollution and for environmental interactions with amyloid peptides,” Finch said. “The findings could extend the benefits of anti-amyloid drugs and treatments to lowering environmental risks of Alzheimer’s disease.”

Finch, who holds the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School of Gerontology, has studied air pollution’s effects on the brain for several years, especially the consequences of exposure to fine particulates found in pollution from automobiles, factories and more. Many studies show that air quality has a sizeable impact on cognitive health, he explained.

“As we work to understand the biology of Alzheimer’s disease and develop interventions for prevention and treatment, efforts to improve air quality will also be critical for reducing cognitive decline and Alzheimer’s,” Finch said.

The post How Does Air Pollution Influence Alzheimer’s Risk? appeared first on USC Leonard Davis School of Gerontology.

The post Aging as a Global Issue appeared first on USC Leonard Davis School of Gerontology.

Cars and factories produce a fine particulate known as PM2.5 that USC-led studies have linked to memory loss and Alzheimer’s disease. Smaller than the width of a human hair, these tiny particles pose a big problem. Once inhaled, they pass directly from the nose up and into the brain, beyond the blood-brain barrier that normally protects the brain from dust or other invaders.

In a research letter published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the USC researchers described how their labs each independently reported indications of recent decreases in neurotoxicity (damage to the brain or nervous system caused by exposure to toxic substances) of PM2.5 air pollution in humans and mice.

University Professor Caleb Finch and Associate Professor Jennifer Ailshire focused on PM2.5 pollution. The small particulate is absorbed both by our lungs and blood. Long-term exposure to PM2.5 has been linked to premature death, particularly in people with chronic heart or lung diseases.

Declines in brain health associated with unclean air in people with less education

Ailshire’s research, published earlier this year in the Journal of Alzheimer’s Disease, showed a strong association between cognitive deficits and air pollution among people with lower levels of education in 2004.

Based on data from the nationwide Health and Retirement Study, her work showed that, when exposed to PM2.5s, adults 65 and older who had fewer than 8 years of education faced a greater risk of cognitive impairment. But one decade later, Ailshire found no such association for study participants.

A likely factor was the reduction in PM2.5 over the prior decade, said Ailshire, an associate professor of gerontology and sociology. Air quality data showed the average annual PM2.5 levels in the study participants’ neighborhoods were 25% below 2004 levels.

Notably in 2014, very few of the study participants lived in places with annual average PM2.5 that exceeded U.S. Environmental Protection Agency air quality standards. This further suggested that the improvements with cognitive decline were linked to a drop in exposure to high pollution among older adults.

“Improving air quality around the country has been a tremendous public health and environment policy success story. But there are signs of a reversal in these trends,” Ailshire said. “Pollution levels are creeping up again and there are increasingly more large fires, which generate a significant amount of air pollution in certain parts of the country. This gives me cause for concern about future trends in improving air quality.”

Improving air quality may have cognitive benefits

Finch’s research on mice, published earlier this year in the Journal of Alzheimer’s Disease, also found evidence of lower neurotoxicity of air pollution over time.

Finch and his research team have studied pollution levels at the same Los Angeles site and their effect on mouse brains since 2009. After 2017, the mice exposed to a tiny, nanoscale version of PM2.5 appeared healthier. Markedly, they showed sharp declines in several factors of neurotoxicity, including oxidative damage to cells and tissues.

During the years that Finch’s and Ailshire’s studies were taking place, the composition of air pollution in the United States was also changing.

From 2000 to 2020, the PM2.5 levels declined nationwide by 41% according to the EPA. In contrast, urban PM2.5 in Los Angeles declined only slightly from 2009 to 2019. While nationwide ozone levels decreased, Los Angeles County ozone reversed the prior trends by increasing after 2015.

Finch and Ailshire emphasize that their findings cannot evaluate the potential benefits of air pollution improvements to the risk of cognitive decline and dementia. Although PM2.5 levels declined nationally from 2009 to 2016, the year-over-year increases that have been observed since 2017 show that improvements in air quality can be reversed, as they were in Los Angeles.

“Our findings underscore the importance of efforts to improve air quality as well as the continued importance of demographic and experimental evaluation of air pollution neurotoxicity,” said Finch.

Finch and Jiu-Chiuan “J.C.” Chen, an associate professor of population and public health sciences at the Keck School of Medicine of USC, had published a study using both human and animal data that showed brain aging processes worsened by air pollution may increase dementia risk. Their research indicated that older women who lived in locations with high levels of PM2.5 suffered memory loss and Alzheimer’s-like brain shrinkage not seen in women living with cleaner air.

The post Clean Air Matters for a Healthy Brain appeared first on USC Leonard Davis School of Gerontology.

Associate Professor of Gerontology and Sociology Jennifer Ailshire joins Professor George Shannon to discuss the impacts of air pollution, global aging and how factors like location and education can influence the way we age.

On the importance of place, or location, on aging

Well, I think of place as one of the greatest supports and constraints on the way that we want to live our lives. So we envision a life for ourselves, our daily decisions, but it’s really dependent on where we live. So for instance, I have a goal to be a very physically fit person and to engage in physical activity every day because I know that’s one of the best ways to support my own health and aging. But if I live in a place where there aren’t a lot of opportunities for me to exercise outdoors, maybe because I don’t have access to good park space or other recreational spaces, maybe because of weather problems, it’s going to have a constraining power on my individual choices. So a lot of people really want to eat healthy and exercise. And some people live in places that provide a lot of opportunities for that. And other people live in places where actualizing those wishes, those goals is really quite difficult. And then of course there are other factors about environments that really matter in terms of social stressors like crime or feeling safe in your neighborhood, and also more physical characteristics like, air pollution, which is one of the things that I’ve spent a lot of time studying while at the school of gerontology here at USC.

On air pollution and aging

We think of air as a physical characteristic. It’s something that exists in the physical environment, but actually, maybe it’s because I’ve been trained as a sociologist. I think of air pollution as a social phenomenon because after all it’s produced by humans for the most part. And so air pollution is located in places where we have a lot of industrial activity and where there’s a lot of car traffic. So some people live in areas where they’re closer to those sources of air pollution, and it usually is the case that those are lower-income communities because throughout much of our kind of industrialized history in this country, people who could afford to live in a nicer area that was further away from sources of pollution would move and they would end up in a cleaner air environment. 

Now here in Los Angeles, we have poor air quality in a lot of places. On average, LA has worse air quality than a lot of cities in the rest of the United States, but there’s also pockets of poor air quality here as well. So by the ports of Los Angeles and the ports of Long Beach, for instance, they have much worse air quality because a lot of that shipping and trucking activity, moving goods around. But living in California these days, particularly during fire season means that a lot of us are going to be exposed to poor air quality at some point during the year. And it doesn’t at that point, it doesn’t really matter what our own socioeconomic resources are. It’s really just ways which way the wind blows and where the fires pop up around us.

Most of the research had been conducted in younger populations in children and adolescents and in younger adults, but just in the past 10 years, it’s become really clear that older adults are a vulnerable population and that they’re more likely to suffer adverse consequences from chronic exposure to air pollution, and also from these acute episodes. So we’ve done a lot of work trying to grow that area of research in public health air pollution topics. And I think that it has really caught on, and there are a lot more people who will have been working in this area, trying to understand the negative impacts of air pollution on older adults. Our group was most interested in the aging brain. And so most of my research has been in trying to understand how air pollution might impact cognitive aging, increasing risk of cognitive decline or risk of cognitive impairment or the onset of dementia, for instance.

I would say that until recently, although people understood that older adults were a vulnerable population, there wasn’t necessarily a lot of direct attention on older adults themselves. So, those of us who work in this area of air pollution and its impact on health among older adults have been saying for a number of years that the federal regulatory standards that are used to regulate air quality,  which had been really successful actually at improving our air quality over the past few decades since these regulations were codified and put into action at state and local levels, they tend to be driven by empirical evidence over the entire life course. They don’t necessarily focus on the evidence for older adults specifically. And the problem that we’ve seen with that is that we tend to find that there are adverse health impacts at lower levels of pollution for older adults than there are for younger adults.

 So I think that we need to have a louder voice as gerontologists, geriatricians, people who are focused on the other end of the life course, that we need to have more of a voice at the table when these conversations are occurring about how we should be improving air quality. And I think that the EPA and state and local organizations are really receptive to this idea because they also see the need for it and the importance of it. I’ve already noted in federal documents that they have been highlighting the need to focus more on older adults. But of course we need that expertise kind of among their ranks. So I’d like to see more partnerships between the environmental sciences side and the policymaker and programming side with gerontologists who are focused on this population.

On the protective role of education

The importance of education for healthy lives cannot be overstated. It is simply the most important factor in all of the research that we’ve conducted and the aging brain is certainly no exception. But actually we think education is particularly important for the brain because we think what happens is that in early life people develop a cognitive reserve or some people call it resilience, but essentially we’re building capacity in the brain to be able to deal with insults that might occur later in life. So for instance, something like building up brain volume or neural connections and early life, which can happen in part through education is really important when an individual gets older and they have exposure to toxic chemicals, for instance, that might cross the blood-brain barrier or enter the brain through other means that having that underlying reserve or that ability to deal with these external threats to brain health is really important.

And people with higher levels of education seem to have a little bit more of that capacity. The other important thing about education though, is that it really sets people up for a lifetime of cognitive engagement. So people who have higher levels of education tend to engage in daily activities that are more likely to operate almost like a brain exercise, but it could be something as simple as playing instruments, speaking other languages and learning new things, taking classes later in life and, socializing with people, but anything that kind of keeps you sharp and keeps you on your feet is another good way to cope with the realities of some of the things that we’re exposed to that might otherwise weaken the health of our brain.

On global aging and Colombia

I think if you ask most people, if you think of a place where there’s aging happening, or there’s a large population of older adults, where are those places? And they would say, think of countries like Japan, the United States, the United Kingdom, some of the countries in Western Europe, but aging is happening everywhere, everywhere, even in lower and middle-income countries like Colombia that we didn’t previously think of in terms of being an aging country. But Colombia, like a lot of countries in Latin America and other countries around the world, is experiencing a couple of key demographic changes like falling fertility rates and increased lifespan. And it’s all happening very quickly. So Colombia will experience the same amount of aging in their population in about 20 years that the United States went through and, you know, in 50 plus years and some countries in Europe did and over a hundred year period. So this is a really opportune time to look at these countries that are undergoing this rapid transition to help us better understand aging. 

I also think that there is a potential to use the unique context of Colombia to help us gain insights, to help us understand aging in the United States population. So some of my colleagues in Colombia are working on a very famous study of genetics and Alzheimer’s disease that are currently the home of one of the world’s most important clinical trials of drugs and interventions for Alzheimer’s disease at the moment. And it’s because they have a cluster of people who are genetically predispositioned to get Alzheimer’s disease at a very young age, in their forties and fifties. And so it’s created this real-world laboratory to understand a disease that we’ve just really been struggling to get a handle on. The discoveries made in Colombia will have far-reaching impacts outside of that country, into the United States and other countries around the world, because we’re all sort of dealing with this impending challenge of an increased number of people in the population who will have some form of dementia in their lifetime.

The post Associate Professor Jennifer Ailshire: the impacts of air pollution, location and education on the way we age appeared first on USC Leonard Davis School of Gerontology.

University Professor Caleb Finch

A new model of aging takes into account not only genetics and environmental exposures but also the tiny changes that randomly arise at the cellular level.

University Professor Caleb Finch introduced the “Tripartite Phenotype of Aging” as a new conceptual model that addresses why lifespan varies so much, even among human identical twins who share the same genes. Only about 10 to 35 percent of longevity can be traced to genes inherited from our parents, Finch mentioned.

Finch authored the paper introducing the model with one of his former graduate students, Amin Haghani, who received his PhD in the Biology of Aging from the USC Leonard Davis School in 2020 and is now a postdoctoral researcher at UCLA. In the article, they propose that the limited heritability of aging patterns and longevity in humans is an outcome of gene-environment interactions, together with stochastic, or chance, variations in the body’s cells. These random changes can include cellular changes that happen during development, molecular damage that occurs later in life, and more.

“We wanted to introduce a conceptual map and some new terminology that will motivate a more comprehensive understanding of what the limitations of genetic determinants in aging are, how important it is to consider the genetic variance in relationship to the environment, and include this new domain of stochastic variations, which is very well recognized by different fields,” said Finch, who holds the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School. “It hasn’t really been put in a formal context in which the complete package can be discussed, and that’s what I hope our article achieves.”

Expanding on the exposome

The new model is a natural extension of the idea of the exposome, which was first proposed by cancer epidemiologist Christopher Paul Wild in 2005 to draw attention to the need for more data on lifetime exposure to environmental carcinogens. The exposome concept illustrates how external factors, ranging from air pollution and socioeconomic status to individual diet and exercise patterns, interact with endogenous, or internal, factors such as the body’s microbiome and fat deposits.

The exposome is now a mainstream model, eclipsing previous characterizations of environmental factors as affecting risk “one by one.” Finch has previously expanded on the exposome concept with the introduction of the Alzheimer’s disease exposome. The gero-exposome now considers how genes and the environment interact over the lifespan to shape how we age.

The new model illustrates that cell-by-cell variations in gene expression, variations arising during development, random mutations, and epigenetic changes – turning genes “off” or “on” – should be explicitly considered apart from traditional genetic or environmental research regarding aging, Finch said. More detailed study into these chance processes has been enabled by cutting-edge research techniques, including the study of gene transcription within single cells as well as ChIP-sequencing, which can illustrate how individual proteins interact with DNA.

The Tripartite Phenotype of Aging is a model describing how genetics, environmental factors, and stochastic, or chance, variations shape longevity.

Effects of happenstance on health

In the paper, Finch and Haghani discussed several examples of how risks of age-related disease are poorly predicted by DNA alone but are heavily influenced by environmental exposures as well as the time and duration of the exposure, including during development or over the course of decades.

One well-known example of a gene that is associated with increased Alzheimer’s risk is ApoE-4; however, having the ApoE-4 gene doesn’t definitively mean someone will get Alzheimer’s. Studies in both mice and humans revealed that ApoE-4 and clusters of related genes interact with exposures such as air pollution or cigarette smoke to influence risk, and Alzheimer’s patients also show differences in their epigenetics as compared to individuals without the disease.

He added that the idea of environmental exposure can stretch farther than many people expect. Disease exposure earlier in life can affect health risks later in life – and across generations.

“The environment that we’re exposed to goes back to our grandmothers because the egg we came from was in our mother’s ovaries at the time of her birth,” he explained. “So that means, in my case, because my grandmother was born in 1878, I might very well carry some traces of the 19th century environment, which included much greater exposure to infectious disease because there were no antibiotics.”

Finch said that he hopes the more comprehensive model on how genes, environment, and random variations over time interact to influence aging prompt a new discussion of what the rapidly developing field of precision medicine needs to take into account to promote healthy aging.

“I think that there will be a much greater recognition in understanding individual patterns of aging,” he said. “We can only define it up to a certain point by knowing the genetic risks; we must have a more comprehensive understanding of the lifetime exposures, environments and lifestyles of an individual to have a better understanding of genetic risk for particular diseases.”

“Gene-Environment interactions and stochastic variations in the Gero-Exposome” was published online in the Journals of Gerontology, Series A in February 2021. The research was supported by National Institutes of Health grants R01-AG051521, P50-AG005142, and P01-AG055367 to Finch and training support to Haghani via T32- AG052374.

The post Beyond genes and environment, random variations play important role in longevity appeared first on USC Leonard Davis School of Gerontology.