January 3, 2011
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The New Science of Stress: Can We Turn Back the Biological Clock?

By Sarah Adler

Elizabeth Blackburn, PhD, in her lab at the University of California, San Francisco.

We all know that stress is not good for us. It makes us look haggard and feel unhealthy. As it turns out, stress is also aging us from the inside out. When we feel stressed, so do our cells. When we feel old, so do our cells.

That’s the bad news. The good news is that with knowledge comes power, and there are ways to mitigate stress and perhaps even turn back the clock, according to a new book that sheds light on UCSF’s groundbreaking research for the general public.  Breakthrough research, some of it conducted at UCSF, has not only shown that the connection between stress and aging can be confirmed down to the cellular level, but also has pinpointed the exact part of our DNA that links stress to aging. New studies are showing that chronic stress has a long-term effect on our overall health by gnawing away at our DNA, accelerating the rate at which our cells age.

Pioneering this exciting research area is UCSF cell biologist Elizabeth Blackburn, PhD, Morris Herzstein Endowed Chair in Biology and Physiology in the Department of Biochemistry and Biophysics. Together with two other scientists, Blackburn won the 2009 Nobel Prize in Physiology or Medicine for their work in discovering telomerase, the enzyme that lengthens and stabilizes telomeres.

Previous stress research focused on cortisol, the stress hormone, and how high levels of cortisol could make us sick – contributing to cardiovascular disease, intestinal diseases and immune system disorders. 

But with recent findings from UCSF, the focus is shifting to how stress can make us old. This research could not come at a better time, as our population is aging, life expectancy is rising and policy debates on health care are at the forefront.

Signs of Aging
Blackburn likes to use the shoelace analogy when explaining telomeres (pronounced TEEL-oh-meers). They are the tips at the ends of our chromosomes that protect our DNA, not unlike the plastic casing at the end of shoelaces, which keep the ends from fraying. Over time, as cells reproduce, our telomeres become shorter and shorter until they become so compromised in length that the reproduction process stops. As this happens, we see signs of aging.

Blackburn’s lab is reporting cause and effect from nongenetic influences, and is finding that chronic psychological stress takes its toll on the telomerase enzyme. Stress reduces the restorative effect of telomeres, decreasing a cell’s capacity for self-renewal.

Together with Blackburn, Elissa Epel, PhD, associate professor in UCSF’s Department of Psychiatry, published a landmark study in the Proceedings of the National Academy of Sciences in 2004, showing that women who experience chronic stress from caring for their chronically ill and disabled children have shorter telomeres. Their research discovered the longer the period of stress, the shorter the women’s telomeres and the lower their levels of telomerase.

The researchers found that genes play a role in telomerase levels, but they could not trace their results to genetics alone. They isolated stress as the external factor affecting the body’s ability to repair itself.

Protecting DNA
UCSF Chancellor Susan Desmond-Hellmann, MD, MPH, has been closely following the findings on the role that stress plays in the earlier onset of age-related disease. She is interested in learning how UCSF can translate complex research findings into tangible ways to promote health to benefit humanity.

As friends and colleagues, Desmond-Hellmann and Blackburn sat down last year for a “Chancellor in Conversation” session held at UCSF. Desmond-Hellmann was curious, on a more personal level, to find out how Blackburn personally manages stress.

“It’s such a cliché: But work hard; play harder. I think it’s really important,” she told Desmond-Hellmann. “I think having intense relaxation is really important, you know, be it going away for a few weeks or be it doing something or other where your mind can do something different.” 

The interest in telomere erosion and its effects on health and life expectancy goes beyond the medical research circle. The Blackburn-Epel research figures prominently in a new and comprehensive look at the impact of stress on our bodies. In her book, Stress Less: The New Science That Shows Women How to Rejuvenate the Body and the Mind (Hudson Street Press; 2010), veteran health and science journalist Thea Singer, also a lecturer in English at MIT, examines cutting-edge research on the impact of stress on our bodies down to the DNA level.

But she doesn’t stop there. She provides tools to help change our lifestyles and embrace DNA-protecting habits. Tips include busting belly fat, remaining positive, exercising regularly, maintaining a social network, meditating and even eating pistachios. A study from Penn State showed that pistachio nuts can reduce our vascular response to stress – specifically, relaxing our blood vessels and causing our blood pressure and our LDL and triglyceride levels to drop.

Singer says it boils down to the issue of control. “What is stressful when we feel we can’t control the circumstances? Maybe we can’t change the circumstances – we can’t make the traffic jam go away – but we can change our perceptions of those circumstances,” she said in a recent interview.

The Blackburn-Epel research formed the cornerstone of Singer’s book,which was named among the top five picks on the Wellness Reading List of The Wall Street Journal. And while working on it, Singer was inspired to adopt her own telomere-promoting practices. When she’s on the treadmill, she’ll often visualize these things happening in her body and use it as a motivator.

“To me,” she said, “that is incredibly motivating – the thought that I can get on the treadmill and doing my aerobic exercise could or would correlate with the lengthening of my telomeres and slowing down my biological aging.” 

Hoping to keep her telomeres long, Singer also changed her relationship to time. Now, when she drives in her daily commute from her home outside Boston to MIT about five miles away, she gives herself more time to get there.

“I have been trying to change my relationship to time,” Singer said. “This perspective came about from me doing the research for this book. We can’t change time; it just marches on. But what we can change is our relationship to time.”

Soon, we may be looking at telomere measurements as a marker of overall health. We may see quick telomere tests being offered as routinely as blood pressure checks. We go to the doctor today to get our blood pressure tested, our cholesterol levels measured and our inflammatory proteins looked at. But wouldn’t it be nice to have a better understanding of where we stand on the biological aging spectrum?

And that is just what the Blackburn lab at UCSF continues to strive for: a more complete understanding of the role of telomeres and telomerase in cell processes. From a recent collaboration with Dean Ornish, MD, investigating whether intensive lifestyle changes would affect white blood cell telomerase activity to examining the reduction of intrusive thoughts (a typical feature of stress) by using meditation, the eventual goal is for patients to make more informed choices about their health to enhance their quality of life.

Moving Discovery to Market
Blackburn is also moving from discovery to industry with the recent launch of a biotechnology company called Telome Health, Inc., which leverages the predictive power of telomere and telomerase assays to assess drug response, health status, and disease and mortality risk.

Blackburn will be speaking on “Puzzles of the Telomere Maintenance System: The Long and Short of It,” at 4 p.m. on Tuesday, Jan. 4 in Byers Auditorium, Genentech Hall, on the UCSF Mission Bay campus. Blackburn’s talk will focus on her research about telomeres and telomerase – both her mechanistic work using cell and molecular biology and her research on the implications of telomere maintenance for human health and disease processes.

On Thursday, March 3, Singer will appear in San Francisco at the Commonwealth Club on a panel with Epel as well as Calvin Harley, PhD, a pioneer in telomere biology who is the chief executive officer of Telome Health, and UCSF’s Jue Lin, PhD, who specializes in perfecting telomere and telomerase assays in Blackburn’s lab.

Photo by Elisabeth Fall/fallfoto.com