The Modern World Is Aging Your Brain

In a remote part of the Amazon, anthropologists and neuroscientists are learning about life and health without an “embarrassment of riches.”

Beside the schoolhouse turned medical station in the northern Bolivian village of Las Maras, everyone is waiting for breakfast. Today’s meal is rice and eggs, generously salted and adorned with globs of mayo: hearty fuel for a workday of foraging and hunting animals. Sheltering from the rain under palms, rubber trees, and a series of large tarps, the people are aged from 40 to 80-plus—all of them Tsimane, an Indigenous group living in the lowlands of the Amazon.

Each has been asked to fast until after they’ve had a voluntary medical exam. Blood draws. Urine and stool samples. Respiratory tests under one tarp; artery stiffness measurements under another. While they wait to speak with a doctor, people give interviews to fellow Tsimane who are collecting anthropological data. Later—if they desire—the interviewees will take a drive to the nearby city of Trinidad to get their brains scanned.

The routine was familiar for Hillard Kaplan, an anthropology and health economics professor at Chapman University in Orange, California, who has been working alongside the Tsimane for 20 years. His life’s work is to study how people in their society age compared to people in the United States and Europe. Between 2014 and 2019, Kaplan led a mobile team of doctors, lab biochemists, and anthropologists—more than half of whom were from the Indigenous population—to more than 100 villages. They collected data from those willing to share it and provided health care to those who wanted it. “Everything is up to the person—what they want to do and don’t want to do,” Kaplan says. About 90 percent of people agreed to participate.

Though some Tsimane interact with broader Bolivian society, their way of life is less industrialized than most. Tsimane villages have no running water, and most have no electricity. They use slash-and-burn agriculture. People hunt on foot for animals such as peccaries—a kind of pig—which means they must expend a lot of energy to simply eat. In some ways, their way of life gives a glimpse into the past. That means a lack of modern health care infrastructure but also, as Kaplan and his team have come to suspect, protection from the ills of urbanized life.

Time, and modern life, take a toll on brains. Cognitive function naturally fades as brain cells shrink and die. Some cells get replaced, yet many don’t, so brains get smaller with age, starting around the time a person turns 40. This atrophy accompanies declines in cognitive function and is a common feature of neurodegenerative diseases like Alzheimer’s or dementia, which affect more than 55 million people worldwide, according to the World Health Organization.

But our fundamental understanding of brain aging has a problem: It’s biased. Far more studies pick apart the aging brain in white, industrialized populations than among racial and ethnic minorities—especially isolated societies. Kaplan and his team want to change that. Their previous work has shown evidence that groups like the Tsimane don’t suffer the same burden of cardiovascular disease as the rest of the world. Could the same be true for the brain? “We didn’t know what we would find,” Kaplan says.

Now, his team has evidence that the brains of the Tsimane and neighboring Moseten people may age slower than yours, mine, and the brains of pretty much everyone else in the industrialized world. “Something about the lifestyle is affecting brain aging,” Kaplan says. He thinks he knows what that something is—and that it can teach us how to better control the aging of anyone’s brain.

Public health in remote societies could enlighten public health elsewhere. Back in the 1980s, Kaplan was working with the Mashiguenga, an Indigenous group who had only recently come into contact with industrialized society in Peru. As Kaplan observed their lives and conducted interviews, people would often ask him for help with health problems. But the young anthropology professor had no medical training.

So he asked a colleague, physician Benson Daitz, to come along to perform checkups. Daitz flew to Peru in 1987 and diagnosed patients with a litany of infections. But he was surprised by what he didn’t find. He heard no murmurs or other cardiac problems. The Mashiguenga had healthy hearts and blood pressure levels, even in old age. Kaplan concluded that they might be spared many chronic diseases. That hunch stuck with him.

Three decades later, Kaplan is still connecting the dots between lifestyle and chronic disease, and he’s still offering health care in villages that host his team and work with them. The people in the villages get their medical needs met; the researchers, in return, get to learn about diseases of the heart and brain.

Over the years, Kaplan’s team has reported that, like the Mashiguenga, the Tsimane have higher than average rates of infection yet lower rates of heart disease and diabetes compared to people in the US and Europe. “These were not conditions associated with aging,” says Daniel Eid Rodriguez, a biomedical researcher with the Universidad Mayor de San Simón, Bolivia, who has worked with Kaplan and the Tsimane since 2004. Nor were these people with healthy hearts isolated cases, says Rodriguez. “The lifestyle of the Tsimane seemed to be the healthy recipe.”

On the other hand, a majority of people in the US today die from diseases of aging. Heart disease, cancer, hypertension, diabetes, and Alzheimer’s accounted for 56 percent of US deaths in 2019. The problem is that industrialized societies are an unnatural environment for humans, full of cheap calories and opportunities to be inactive.

Kaplan’s team wanted to see if a non-industrialized life versus a modern, industrialized life would also benefit the brain. For their latest paper, published in March, Kaplan continued his ongoing partnership with the Tsimane and started a new one with the nearby Moseten, a rural Indigenous group that farms more and is more involved in modern markets than the Tsimane. The Moseten are less dependent on hunting and foraging—meaning they don’t have to work as much for their food. All the participants the team studied were over 40, because that’s when scientists expect the brain to age more noticeably.

After the daily breakfast and data collection sessions, participants would go to a nearby hospital, where specialists would image their brains and chests with CT scanners. Brain scans would yield a total volume of brain matter for each person; chest scans would reveal deposits of fat and calcium in and around the heart. The team also collected data from people like their height, body mass index, and cholesterol.

Four years and 1,165 participants later, the results revealed a stark difference. When compared to similar data taken from the US and Europe, the Tsimane fare much better, especially in old age. Tsimane brains lose about 2.3 percent of their volume per decade, compared with around 2.8 percent for the Moseten and about 3.5 percent for industrialized populations. For septuagenarians and older, the difference nearly doubled.

In industrialized populations, brain volume usually drops with increasing body mass index and non-HDL (so-called “bad”) cholesterol. But Tsimane and Moseten brain volumes largely increased with rising BMI and cholesterol. Kaplan believes this discrepancy makes sense given humankind’s evolutionary past. If you have to work a lot to get your food, more energy actually helps. The Tsimane walk 17,000 steps per day.

Older Tsimane provide food and care for their grandchildren and don’t really retire, Kaplan says. People who live in the US and Europe on average work much less for their calories, which creates a surplus.

To Kaplan, the new data suggests a “sweet spot” between energy in and energy out and that it’s fine to build up a higher BMI if you expend a lot of energy too. But without that balance, you may lose brain volume faster, perhaps due to poorer cardiovascular health—although the exact mechanism remains unclear. “We’re at the point where we’ve overshot the mark,” he says of industrialized populations. “We have too many calories, too little physical activity, leading to negative effects on our brains.” The team refers to the phenomenon as the “embarrassment of riches” hypothesis.

“I imagine that the same logic will be valid for other non-communicable diseases among the Tsimane where there is a strong metabolic component,” says Rodriguez. “That is, the food reflected in the BMI and cholesterol is important for the body to carry out its activities, but in excess it is ultimately harmful.”

While this is the first study to compare brain volume between people in such different societies, others have pointed out the link between exercise and dementia risk. Studies estimate that the risk of dementia drops by at least 30 percent for physically active adults. Exercise may reduce inflammation in the brain and sustain hardier connections (or synapses) between neurons. Last year, researchers autopsied US participants of an aging and cognition study, and discovered that those who exercised more had higher levels of biomarkers tied to synaptic function.

“We’re starting to understand that these behaviors that we engage in can change how our brain develops,” says Kaitlin Casaletto, a neuropsychologist at the University of California San Francisco, who led the autopsy study but was not involved in Kaplan’s work. “Maybe we can play an active role in how our brain develops with age.”

Casaletto says that Kaplan’s work with Tsimane and Moseten populations addresses an important representation problem in aging and brain science—that most people studied are white and live in industrialized societies. But while the findings broaden our understanding of brain shrinking, it also brings a lot of new questions too, she says.

“I would want to know if the positive relationship between BMI and cholesterol with brain volume differs by age,” she says. In other studies, involving US and European participants, the relationship evolves: high BMI in middle age indicates bad brain health, but low BMI in old age tracks with frailty and dementia. Overall, Casaletto finds the embarrassment of riches hypothesis “compelling” and worthy of more testing.

Still, a tricky thing about comparing such different societies is that researchers are only evaluating who actually survives to old age. It’s a bias inherent to many aging studies. And in Bolivia, Indigenous populations have higher rates of early death, primarily due to infections. “The adults that made it to this point may not be representative of the whole population,” Casaletto says. “They may have certain genetic or social or other biological advantages.”

Genetics may play in Kaplan’s data, adds Tamar Gefen, a neuropsychologist with Northwestern University who was not involved in the study. Gefen has worked with Northwestern’s SuperAging study, which follows people over age 80 whose brains function like those of people decades younger. The brains of the superagers in the study shrank less than those of “cognitively average” elderly people. Many superagers don’t have healthy lifestyles, but they still stay cognitively sharp. This suggests genetics may be crucial to brain health and that physical activity isn’t a panacea. Superaging studies also suggest that being social, happy, and exercising your mind all play a role in keeping the brain healthy. But each factor relates to the other: It’s easier to be happy and social if you’re healthy, for example.

To Kaplan, the implication is that we need to better understand both the physiology and psychology at play in healthy aging. How to strike that balance of energy in and out is valuable for overall health. “That’s what we need to understand more,” he says. “I think there are many people in the US who are living close to that optimal sweet spot. But many people are failing to achieve it.”

Back in Bolivia, the Tsimane population has recently begun integrating more, thanks to cheaper canoe motors. There are benefits to integration, Kaplan notes, like easier access to food. “The modern lifestyle is more comfortable,” Rodriguez adds. “Even though they are conscious that their lifestyle can be healthier, it’s full of limitations related to transport, trading, health care access, education.”

More integration also means people may get closer to health care; doctor visits once held in thatch-roofed schools may give way to more frequent trips to the city. But as the population modernizes, there’s always the chance that the Tsimane will succumb more frequently to ailments common in industrialized society. It’s even possible the condition of their brains may start to change. Whatever happens, Kaplan and Rodriguez know that there’s much more to learn.

Source