(Credit: Jacob Lund/Shutterstock) The Nicoya peninsula in northwestern Costa Rica is one of the most beautiful places on the planet. This 75-mile sliver of land, just south of the Nicaraguan border, is covered with cattle pastures and tropical rain forests that stretch down to the crashing waves of the Pacific Ocean. The coastline is dotted with enclaves of expats who fill their time surfing, learning yoga and meditating on the beach. For the locals, life is not so idyllic. They live in small, rural villages with limited access to basics such as electricity, linked by rough tracks that are dusty in the dry season and often impassable when it rains. The men earn a living by fishing and farming, or work as laborers or sabaneros (cowboys on huge cattle ranches), while the women cook on wood-burning stoves. Yet Nicoyans have a surprising claim to fame that is attracting the attention of scientists from around the world. Their secret was uncovered in 2005 by Luis Rosero-Bixby, a demographer at the University of Costa Rica in San José. He used electoral records to work out how long Costa Ricans were living, and found that their life expectancy is surprisingly high. In general, people live longest in the world’s richest countries, where they have the most comfortable lives, the best health care and the lowest risk of infection. But that wasn’t the case here.
The Nicoya peninsula in Costa Rica. (Credit: Hugo Brizard/Shutterstock) Costa Rica’s per capita income is only about a fifth that of the U.S., but if its residents survive the country’s relatively high rates of infections and accidents early in life, it turns out that they are exceedingly long-lived — an effect that is strongest in men. Costa Rican men aged 60 can expect to live another 22 years, Rosero-Bixby found, slightly higher than in Western Europe and the U.S. If they reach 90, they can expect to live another 4.4 years, six months longer than any other country in the world. The effect is even stronger in the Nicoya peninsula, where 60-year-old men have a life expectancy of 24.3 years — two to three years longer than even the famously long-lived Japanese. Nicoya is one of the country’s poorest regions, so their secret can’t be better education or health care. There must be something else. Another longevity expert, Michel Poulain of the Estonian Institute for Population Studies in Tallinn, traveled to Nicoya with the journalist Dan Buettner in 2006 and 2007 to investigate Rosero-Bixby’s findings. The pair were working for the National Geographic Society, identifying long-lived communities around the world — which they dubbed “Blue Zones”—and attempting to work out their secrets. Other examples included Sardinia, Italy, and Okinawa, Japan. In Nicoya, Poulain and Buettner met people like Rafael Ángel Leon Leon, a 100-year-old still harvesting his own corn and beans and keeping livestock, with a wife 40 years his junior. Living nearby was 99-year-old Francesca Castillo, who cut her own wood and twice a week walked a mile into town. And there was 102-year-old Ofelia Gómez Gómez, who lived with her daughter, son-in-law and two grandchildren. When Buettner’s team visited, she recited from memory a six-minute poem by Pablo Neruda. All of the elderly people they saw were still mentally, physically and socially active, despite their advanced age. Poulain and Buettner drew up a list of things that might be helping Nicoyans to age so well. They have active lifestyles, even in old age. They have strong religious faith. The lack of electricity for lighting means they go to bed early, sleeping an average of eight hours a night. They drink calcium-rich water (which is good for the heart) and eat antioxidant-rich fruits.
In the Telomeres
Although the project was intriguing, it couldn’t narrow down the crucial factors. But Rosero-Bixby has recently carried out a study aiming to do just that. He teamed up with David Rehkopf, an epidemiologist at Stanford University in California. The pair took blood samples from around 600 elderly Costa Ricans, including more than 200 from Nicoya. They sent the blood samples to Elizabeth Blackburn’s lab in San Francisco, where she measured the length of their telomeres. If the Nicoyans really were aging more slowly, it should show up in her results.
Human chromosomes with telomeres highlighted in white. (Credit: U.S. Department of Energy Human Genome Program) The team reported in 2013 that Nicoyans’ telomeres are indeed longer than those of other Costa Ricans. Their impressive life expectancy isn’t a statistical fluke but a real biological effect, in which their cells look younger than expected for their age. The size of the effect was equivalent to changes caused by behavioral factors such as physical exercise or smoking. To investigate why the Nicoyans’ telomeres are so long, Rosero-Bixby and Rehkopf analyzed the effects of everything from the residents’ physical health and level of education to their consumption of fish oils. Diet makes no apparent difference, and the Nicoyans are worse off than other Costa Ricans when it comes to health measures such as obesity and blood pressure. Their slower aging doesn’t seem to be a consequence of genes either — Nicoyans lose their longevity advantage if they move from the region. And it isn’t money: richer individuals actually have shorter telomeres. But there are some clues. Rehkopf and Rosero-Bixby found that Nicoyans are less likely than other Costa Ricans to live alone, and more likely to have weekly contact with a child. Such social connection seems crucial. The telomere length difference is halved among Nicoyans who don’t see a child each week, and if they live alone, they lose their advantage completely. Other studies have found that Nicoyans have greater psychological attachment to family than residents of Costa Rica’s capital, San José. So Rehkopf and Rosero-Bixby speculate that close family ties might protect Nicoyans against life stress that would otherwise shorten telomeres. Despite their poverty, strong social bonds keep them young. It’s a startling finding, and to confirm it will take studies that collect more detailed data about the Nicoyans’ social connections. But Poulain says the theory fits with his own observations. He emphasizes (as does Rehkopf) that there is no single secret to long life, and that residents of longevity hotspots such as Nicoya probably enjoy a lucky combination of genetic and environmental factors. Yet he has seen unusually strong social networks in other Blue Zones too. “The social aspects are crucial,” he says. “There’s terrific support for the elderly.”
The idea is also bolstered by decades of evidence from communities suffering the reverse phenomenon: the gradual loss of social ties. When we’re away from someone we love, we say that it hurts. You might think of this description as metaphorical; brain-scanning experiments suggest, however, that it’s uncannily accurate. It turns out that experiences of social exclusion or rejection — such as being shunned in a game, receiving negative social feedback, or viewing images of deceased loved ones — activate exactly the same regions of the brain as when we are in physical pain.When we’re socially rejected or isolated, we don’t just feel sad. We feel injured and under threat. Likewise, stress researchers have found that our bodies respond to social conflict — being criticized or rejected by others — in the same way we respond to imminent physical harm. It’s no coincidence that one of people’s most common fears is public speaking, or that one of the most effective tools psychologists have for triggering the fight-or-flight response, the Trier Social Stress Test, requires volunteers to perform in front of a panel of stone-faced judges. Carrying out similar tasks when nobody’s watching is nowhere near as stressful.
(Credit: Shutterstock/Christian Mueller) The lack of social ties, although less acute, can be just as toxic over time: even if they score low on conventional measures of stress, lonely people have high baseline levels of stress hormones and inflammation, with all of the health problems that entails.Social support also seems to shield us against difficult circumstances — those without it are much more susceptible to other stresses when they come. But why do social rejection and isolation affect us so dramatically? Having no friends might not be pleasant, but it’s hardly a matter of life and death. That’s where I’m wrong, says John Cacioppo, a psychologist at the University of Chicago, Illinois, and probably the world expert on loneliness. He points out in his 2008 book, Loneliness, that for most of human history, becoming separated from others put us at imminent risk of starvation, predation or attack. Social isolation was indeed a death sentence, as much a threat to our survival as hunger, thirst or pain. As a result, we’ve evolved to be so desperate for human contact that if deprived of it we can even form attachments to inanimate objects, like Tom Hanks’s character in the movie Castaway, who has a meaningful relationship with a volleyball he calls Wilson. But you don’t need to be marooned on a desert island to feel lonely. If we don’t feel cared for, we can feel lonely even when surrounded by others: at college; on a crowded bus; in a strained marriage. After all, being among a hostile tribe is just as dangerous as being alone.
The Downside of Flying Solo
The impact of loneliness, then, depends not on how many physical contacts we have but how isolated we feel. You might have only one or two close friends, but if you feel satisfied and supported there’s no need to worry about effects on your health, Cacioppo tells me. “But if you’re sitting there feeling threatened by others, feeling as if you are alone in the world, that’s probably a reason to take steps.” Such “loneliness in a crowd” is an increasing problem in modern society as we move around, often living far from family and friends. Studies in Western countries suggest that 20 to 40 percent of adults are lonely at any one time, with one of the loneliest populations studied being college freshmen. Most of us soon reach out to others or our circumstances change. But 5 to 7 percent of people report feeling intensely or persistently lonely. One reason for their plight is that, like stress, chronic loneliness reshapes the brain, in this case making people more sensitive to social threat. Lonely people rate social interactions more negatively, are less trusting of others, and judge them more harshly. There’s an evolutionary logic to this too: in a hostile social situation it is vital to be alert to betrayal and potential harm. But it can make lonely people reluctant to reach out to others. Feeling threatened also disrupts their social skills, says Cacioppo, leaving them focused on their own needs at the expense of anyone else’s. “When you talk to a lonely person you feel like they are feasting on you,” he says. “Not in a good way.”
Down to Our DNA
In 2007, Cacioppo published a result that opened a new window into how our physical makeup is influenced by the contents of our minds. He showed that stress—especially social stress—doesn’t just affect the brain. It filters right down to our DNA. From a group of 230 elderly Chicagoans, Cacioppo selected eight of the loneliest, who had felt isolated for several years, and six of the most connected, who reported that they had great friends and social support. He sent samples of their blood to molecular biologist Steve Cole at the University of California, Los Angeles, who analyzed which genes were active in each group. The pattern of gene expression varies in different cell types, so Cole focused on the white blood cells of the immune system, because what these cells do — whether they cause inflammation or produce antibodies, for example — is crucial for health. The Chicagoans’ social worldview had a dramatic effect on what was happening inside their cells. Of about 22,000 genes in the genome, Cole found significant differences in more than 200—which were either activated to produce more of a particular protein, or turned down to produce less. Individual genes might look different by chance; what was striking, says Cole, was the broader pattern.
(Credit: Lissandra Melo / Shutterstock) A large proportion of the lonely people’s up-regulated genes were involved in inflammation, whereas many of their down-regulated genes had roles in antiviral responses and antibody production. In sociable people, the reverse was true—biological activity in their immune cells was skewed towards fighting viruses and tumor cells and away from producing inflammation. Crucially, the difference related most strongly not to the actual size of the volunteers’ social networks but to how isolated they felt themselves to be. It was a very small study, but one of the first ever to link a state of mind with a broad, underlying change in gene expression. The result suggests that our immune system is fine-tuned to respond to our social surroundings. It makes perfect sense that we evolved this way, says Cacioppo. In the past, people in a close-knit group would be at risk from viruses, which spread easily between individuals in close contact, or—because they would likely survive longer—from longer-term conditions such as cancer. An isolated person, by contrast, would have more to fear from physical attack, so their survival would depend on triggering branches of the immune system involved in wound healing and defense against bacterial infection. In today’s world, however, this gene expression profile is a double whammy, increasing the risk of chronic inflammation-related conditions while leaving us more susceptible to viruses and cancer.
Replicating Results
The researchers have since replicated that preliminary result in a larger sample,^ and Cole has seen the same effect in other types of social adversity in humans and other primates, from macaques placed in unstable social groups, to people caring for dying spouses. Cole is now starting to test whether it’s possible to reverse this adverse genetic profile. For example, a 2012 trial of 79 women recently diagnosed with breast cancer found that group stress-management therapy reduced expression of inflammation-related genes and pushed women back towards an anti-viral profile. “Our conclusion was that mood matters,” says Michael Antoni, of the University of Miami, Florida, who led the study. Not everyone agrees, in particular James Coyne, a health psychologist and emeritus professor at the University of Pennsylvania in Philadelphia and prominent skeptic of positive psychology. Particularly when it comes to cancer, researchers who claim that psychological factors can influence disease progression put pressure on patients, he argues, and risk blaming those who don’t recover for not thinking in the right way or attending the right classes. “They claim that if you make the right choices, you’ll be healthy. And if you don’t, you’ll die.” Whether social support helps cancer patients to live longer has been controversial ever since Stanford psychologist David Spiegel found that group therapy doubled survival time in a 1989 trial of 86 women with metastatic breast cancer. There have been plenty of attempts since to replicate that result, of which eight concluded that therapy does improve survival and seven have found no difference.^ Results from epidemiological studies are mixed too, but in 2013, Harvard researchers who followed 734,000 patients found that for all the cancer types they looked at, people who were married were 20% less likely to die from their cancer, even after controlling for practical advantages such as help getting to appointments and taking medication on time. Overall, Spiegel claims the balance of evidence is in favor of there being a significant effect on survival, whereas Coyne concludes that “the whole idea that psychological factors can affect the lives of cancer patients is rubbish.” He describes Antoni’s trials as too small to show anything useful and like researching the money you get from the tooth fairy: investigating a mechanism when it hasn’t been established that there’s an effect to be explained. “Everything we’re doing is preliminary,” responds Antoni. “We do need to be cautious. But each year, studies are showing results in a similar direction. They are showing that if we change the psychology, physiological changes do parallel that.” Antoni is now following 200 women for up to 15 years after receiving therapy, to see if this has any effect on cancer recurrence or survival time.
Excerpted from "Cure: A Journey Into the Science of Mind Over," by Jo Marchant, published by The Crown Publishing Group, Copyright © 2016 by Jo Marhcant. Used by permission. All rights reserved.
