How chronic stress is harming our DNA

We hear about how bad stress is for our health, but just how bad is it? This article sheds some important light on this issue. It is more important than ever to address your chronic stress through exercise, self care activities, social support and even therapy.

Elissa Epel is studying how personality, stress processes and environment affect our DNA — and how we might lessen damaging effects.

By Stacy Lu

October 2014, Vol 45, No. 9, Print version: page 28

Money problems, a heavy work load, caregiving — such increasingly common pressures have helped make stress a part of modern American life. According to APA's Stress in America survey, 42 percent of adults in the United States. say their stress level has increased over the past five years. Even teens reported stress rivaling adult levels.

Recent research suggests chronic stress damage starts before we're even conceived and cuts into our very cells. A number of studies have linked stress with shorter telomeres, a chromosome component that's been associated with cellular aging and risk for heart disease, diabetes and cancer.

How do personality and environment play into this phenomenon? Elissa Epel, PhD, has been exploring that question for more than a decade at the University of California, San Francisco, where she directs the Center for Aging, Metabolism and Emotion. She often works with Elizabeth Blackburn, PhD, who won a Nobel Prize in 2009 for her research on telomeres.

Epel talked to the Monitor about her quest to understand stress and what might help lessen its effects.

What are telomeres and how are they related to aging and disease?

Telomeres are a protective casing at the end of a strand of DNA. Each time a cell divides, it loses a bit of its telomeres. An enzyme called telomerase can replenish it, but chronic stress and cortisol exposure decrease your supply. When the telomere is too diminished, the cell often dies or becomes pro-inflammatory. This sets the aging process in motion, along with associated health risks.

How does stress rank in terms of factors that affect telomere length?

The two biggest factors are chronological aging and genetics, but stress is now on the map as one of the most consistent predictors of shorter telomere length. The type of stress determines how big its effect is. It seems exposures to multiple early life adversities, such as child neglect, have the largest effects, since they track through to late adulthood, or they set in place persistent mechanisms that maintain short telomeres throughout life, such as exaggerated stress reactivity and poor health behaviors. Stressors such as caregiving in late life also have an effect. So we can see this relationship between stress and cell aging across a lifespan, and it's fundamental to how we're built. Our brains are constantly looking for threats to our survival. When we expose our bodies to years of chronic stress arousal, we see effects that override normal aging, making our telomeres look like they are from a significantly older person. When we look at groups of people with psychiatric disorders related to dysregulated emotional responses, especially depression, and compare them to controls who have never experienced these disorders, they consistently have shorter telomeres.

How early in life do the negative effects of stress begin?

If you want to be literal about it, it starts before conception. A baby's intrauterine environment is shaped by a mom's pre-existing physical health. There have also been several studies looking at maternal health and telomeres in offspring. So far, we found in a small study that the higher a mom's prenatal anxiety, the shorter the baby's telomere length, as seen in the work of Sonja Entringer, PhD, Pathik Wadhwa, PhD, and others. This scenario is setting the stage for an accelerated trajectory of aging. It may, in fact, be one of the most critical periods in time for impacting cellular aging. Transgenerational transmission of risks has to be taken into account for understanding and improving public health.

Another consistent pattern turning up in both clinical and epidemiological samples is that early life adversity is associated with shorter telomeres. This relationship was first observed in adults when early adversity was assessed retrospectively, but now it has been observed in young children prospectively. Maltreatment, abuse, severe neglect and exposure to violence all seem to take a swath from the telomeres.

The good news is that there are buffers to early adversity, such as warm and interactive high-quality parenting, or possibly the luck of having a more stress-resilient genotype, according to a small study by Colter Mitchell, PhD, and colleagues.

One of your recent studies has the intriguing finding that stress may alter how we metabolize high-fat, sugary foods. What's behind that?

Ah, yes. There is a somewhat involved story here. Chronic stress wreaks havoc in neurally driven compulsive eating patterns. It can cause neuroplastic changes that alter how we perceive and react to the world in ways that might be good for short-term survival but not for longevity mechanisms. Stress impairs our executive function, which dampens our ability to resist impulses. Chronic stress can increase the reward responsiveness of our brains. So if we are at all prone to addiction, it's going to make us crave palatable food or drugs even more. It drives us to choose comfort foods, whether unconsciously or with a strong intention. Now what's happening in the body? We know that people with high stress develop greater levels of abdominal fat. Mouse models have shown that pathway. The combination of high stress and [eating a lot of] junk food works synergistically here. Stress leads to neuropeptide Y (NPY), a chemical that triggers the intra-abdominal fat cells to mature and fill up with more fat. Assistant professor Kirstin Aschbacher, PhD, and I examined this in humans and found the suspected pattern. The high-stress caregivers who ate more comfort food had higher NPY and abdominal fat. But this was not observed in the caregivers with the healthier diet, nor in the low-stress controls with the junk food diet. In our next study we are putting high- versus low-stress people on a high sugar diet, short term of course, to test these effects more experimentally.

After the rodent study that looked at NPY, there was a flurry of excitement: "Can we block NPY and the stress-fat relationship?" I think this is unlikely. There are multiple stress pathways, so we'd have to block stress at its source, which is how we perceive events. Otherwise, you're putting a little Band-Aid on the robust positive feedback loop between stress biology and fat cells. That's a major survival mechanism, and I doubt it can be blocked by just one chemical pathway.

What else are you working on?

Our group, including my co-principal investigators Nancy Adler, PhD, and Barbara Laraia, PhD, has taken on the study that excites us the most: an intervention that helps overweight, low-income, pregnant women turn their health around, for themselves and their babies. We want to take advantage of pregnancy as an important "teachable moment" when motivation is high and when the mental and physical health of the next generation is being formed. But this has turned out to be the most challenging intervention we've run as well.

We've developed a mindful stress reduction/mindful eating class to reduce stress and excess weight gain during pregnancy. Despite these women's high motivation, there are structural factors that prevent them from meeting their goals. There are too many unpredictable stressful and even traumatic events embedded in their neighborhoods and social environments that continue when they're pregnant. They witness or experience violence. One of our participants was even shot in a limb while pregnant. The developing babies are exposed to all of this.

A class alone also can't change critical aspects of their food environment, including food insecurity — the stressful state of not having enough money to feed yourself and family. Our class can help them reduce their levels of depression and stress, which has meaningful biochemical sequelae, but helping them prevent excess weight gain may take more of a systemic village effort and must start earlier than mid-pregnancy to influence the health of the next generation.

I am also very focused on improving stress reduction interventions through adaptive emotion regulation — partly through mindfulness-based techniques. I have studies at residential retreat centers, as well as a study trying to teach parents mindfulness skills. While general mindfulness training is helpful and can be transformative to some, there are many ways to use it to tailor treatments, to use technology to bring awareness to one's busy day.

We are also testing the effects of aerobic exercise on telomerase in sedentary young adults — the work of assistant professor Eli Puterman, PhD, of UCSF. Exercise is probably the biggest antidote to biological stress dysregulation — excessive cortisol, insulin, inflammation and oxidative stress that make up a "stress soup." Eli has shown cross-sectionally that exercise moderates the stress-telomere relationship, and he recently published the first demonstration of what appears to be longitudinal lifestyle stress buffering. If you have a really stressful year, yes, your telomeres may take a hit, but not if you are doing the daily work of health maintenance — exercising, eating fruits and vegetables, and getting enough sleep. If you've got those habits, your telomere attrition looks like someone who glided through the year with no big stressful events.

Which risk factors for chronic stress do you think are most underappreciated?

Our social environment. How rich is your social fabric? How connected are you to the people in your social circle, starting with your family? A strong social network is probably the biggest buffer from toxic stress, next to exercise. Yet we often lack quality long-term social connections. There is frequent loneliness among high-risk groups like the elderly, who may be more isolated. For those of low income, many are working long and inflexible hours. Part of the problem is that there are limited minutes in the day, and if you are overworking, you are undercaring for your social network and for yourself.

You're starting a non-profit within UCSF dispensing tests that measure telomere length. Won't it be more stressful to find out you have short telomeres than not to know at all?

We've seen the value of telomere length as a predictor for age-related diseases. Many findings indicate it may be possible to build on that to monitor and even prevent disease rather than wait until we get news of some diagnosis we can't change. We are learning that many people want to quantify themselves and track their behaviors. Maybe knowing your telomere length and how it is changing each year could be helpful. Maybe it's worse to know. We just don't know yet.

We plan to host a large group experiment whereby people measure their telomeres at low cost over time, and provide data on the behaviors, medications, events and so on that may be affecting rate of change over time. By crowdsourcing data in this way, we can learn more about the dynamics of change in real life. Will such knowledge be empowering and motivating, and will people's efforts to lengthen telomeres even help? So far, one of our small controlled studies suggested it's not too stressful to learn you are on the short end. People want to know their telomere length, with responsible interpretation of their risks. So we're interested in answering that question more thoroughly: How useful is this measure to individuals?

You're a mother with a demanding job managing diverse projects in multiple areas. How does that affect your own stress levels, and how do you cope?

Work stress is much more of the positive "challenge" stress than "threat" stress. It's gratifying to mentor, help people find their research identities, and get to work with wonderful collaborators and be part of the discovery process across a range of topics. But inevitably, there is too much to do with too little time. No researcher I know of escapes that. If you stay in this business, you can learn to manage that, somewhat with strategy and somewhat with mindset, so it doesn't eat away at you.

The true stress for me comes from parenting a child with special issues. Because of this, I have a good sense of the inside experience of the young and elderly caregivers I study. Compassion for their situations fuels my drive to improve interventions for caregiving stress, such as by developing tailored mindfulness classes.

One thing to remember about chronic stress is that it's only our thoughts that make it seem so. Viewed mindfully, no situation is truly chronic — there are always calm moments to notice and be present for. Moments that can be lived in with ease.

Stacy Lu is a journalist in Falls Church, Va.

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