Does Reducing Stress Impact Telomere Length?

So you’re stressed. You are not alone – the American Psychological Association’s 2015 Stress in America Survey reports that 78% of American adults reported having experienced at least one symptom of stress last year. As we reviewed in my last blog post, there is a considerable body of research that associates chronic stress exposure with telomere length.

Research on whether and how lifestyle change interventions that aim to reduce stress also change telomere length is still in its early stage. Below, I have summarized some of the various pilot studies that address this question. In three of the below studies, the authors measured telomerase activity as a potential mechanism an indirect proxy for telomere growth. It therefore warrants a brief overview of the functional role of the enzyme telomerase in the growth and maintenance of telomeres.

Telomerase activity is crucial for preservation of telomeres’ function and structure. Technically speaking, telomerase is an enzyme made of protein and RNA subunits that that restores telomeres by adding TTAGGG telomeric DNA sequences when they are shortened due to mitosis, or cell division or other reasons. When the cell’s telomeres become critically short, the cell becomes senescent and cell division stops. Telomerase replaces the bit of DNA lost in each cell division, allowing the cell line to divide without ever reaching the limit. The below studies that look at stress reduction activities and their impact on telomeres use both telomere length measurement and telomerase activity levels to assess association.

In a paper published in 2008 by Dean Ornish and others in Lancet Oncology, 30 men with biopsy-diagnosed low-risk prostate cancer were recruited to participate in a comprehensive lifestyle change program. The program included a low fat, whole foods, plant-based diet high in fruits, vegetables, unrefined grains, legumes, and low in refined carbohydrates; moderate aerobic exercise, stress management (gentle yoga-based stretching, breathing, meditation, imagery, and progressive relaxation techniques), and group support sessions. Telomerase activity was measured at the baseline before the start of program and after 3 month from peripheral blood mononuclear cells (PBMCs). There was a statistical significant increase in telomerase activity after 3 month of comprehensive life style change. More importantly, increase in telomerase activity is associated with a decrease in lipoprotein (LDL) cholesterol and psychological distress.

In a follow-up paper by the same authors, PBMC telomere length was measured from the baseline (before the start of the lifestyle change program) and 5 years later in ten men from the 2008 study cohort.  After the three months program, the participants could meet on their own for 2-4 hour meetings per month for the duration of the study with a physician or nurse on site. The control group consists of 25 men with low-burden prostate cancer who had chosen active surveillance rather than conventional treatment (for reasons unrelated to the study). Telomere length was measured with the qPCR method. Average telomere length increased from baseline to 5 years in the lifestyle intervention group, but decreased in the control group as expected. Adherence to lifestyle changes was positively associated with telomere length after adjustment for age and the length of follow-up. This is the first intervention study that has shown a significant change in average telomere length when compared with a non-intervention group. I should point out that this is a non-randomized, pilot study with a very small sample size, and the comparison group came from a different study (although with the same inclusion, exclusion criteria). So larger size, randomized studies are needed to test if the results can be replicated.

Meditation is widely accepted as a way to reduce psychological stress and enhance well-being. However, the mechanistic links between meditation and its psychological and physical benefits are poorly understood. Recent studies suggest telomere maintenance maybe one of the cellular systems that is impacted by meditation. In the journal Psychoneuroendocrinology, Jacobs et al reported the effects of a three-month intensive meditation retreat on telomerase activity.

The participants were sixty men and women (aged 21-69) recruited to study the relation between meditation and well-being. They were matched on demographic variables (sex, age) and meditation and randomly assigned to either an on-site, three month meditation retreat or a wait-list control group. The meditation retreat was instructed by Alan Wallace, Ph.D., a well-known Buddhist scholar and practitioner. The meditation focuses on the cultivation of attentional skills and the generation of benevolent mental states. Telomerase activity was measured from PBMCS after the 3-month retreat in the participants and in the control group who were on the waiting list and were about to start the retreat. Psychological assessments included mindfulness, purpose in life and perceived control and neuroticism, measured at baseline and after 3 months. Mindfulness was surveyed by the 37-item Five Facet Mindfulness Questionnaire (FFMQ), which assesses five facets of Mindfulness (observing or noticing experience; acting with attentional awareness or avoiding automatic pilot; non-reactivity to internal experience; describing or labeling feelings; nonjudging of experience). Purpose in Life was measured by a 9-item questionnaire as part of the Well-Being Scale designed by Dr. Carol Ryff that assesses changes in a person’s sense that life is meaningful, organized around clear aims, and clearly directed. Perceived Control was measured by the 9-item Environmental Mastery subscale within the Well-Being Scale to measure perceived control over situations and circumstances.

As expected, retreat participants scored higher on the mindfulness, purpose in life and perceived control questionnaires and lower on the neuroticism score after 3 months. Telomerase activity is higher in the retreat group compared to the waiting-list control group. Using a statistical tool called mediation analysis, the authors showed that the group difference in telomerase activity can be explained by changes in Perceived Control, Neuroticism, and Purpose in Life suggesting that the intensive meditation program affects telomerase activity through improvement in Perceived Control, Neuroticism, and Purpose in Life scores.

In another study by the same group of authors, participants were enrolled in a one-month Insight meditation retreat, a mindful-based mediation program in the Buddhism tradition. Telomere length was measured in PBMCs at the beginning of, and three weeks into the retreat in 26 participants. The control group has 30 age-, gender-, and meditation-experience matched participants who also provided blood at baseline visit and 3 weeks after. While the two groups did not differ at baseline; the retreat group’s telomeres were significantly longer at three weeks than at baseline, whereas the control group showed no change. This pilot work provides the first evidence that a short, but intensive mediation program is associated with telomere lengthening.

Another study led by Dr. Helen Lavretsky at UCLA examined the effects of brief daily yogic meditation on mental health, cognitive functioning, and telomerase activity in family dementia caregivers with mild depressive symptoms. Forty-nine family caregivers who were taking care of their relatives with dementia were recruited in the study. They were randomized assigned to participate in either Kirtan Kriya yogic practice or a relaxation practice for 12 minutes per day for eight weeks. The Kirtan Kriya practice is an ancient chanting yogi meditation involving repetitive finger movements or mudras, as well as chanting of the mantra “Saa, Taa, Naa, Maa,”meaning “Birth, Life, Death, and Rebirth” that are chanted first aloud, then in a whisper, and silently for the total of 11 minutes with 1 minute allocated to “tuning in” at the beginning and the final deep breathing relaxation accompanied by the visualization of light.

The control group was asked to relax in a quiet place with their eyes closed while listening to instrumental music on the relaxation CD for 12 minutes every day at the same time for eight weeks. Telomerase activity was measured in PBMCs at baseline and after 8 weeks in both groups. A battery of psychological assessments was also administered. The Mental Health composite score (MCS score) assessed health-related quality-of-life, mental, physical, and social functioning. The Hamilton Rating Scale for Depression was used to quantify mood symptoms. The Mini-Mental State Examination (MMSE) was used to measure cognitive performances. The yogic practice group had improved Mental Health Summary (MCS) score and cognitive function and decreased depression score. The meditation group had increased telomerase activity, compared to no change in the control group. More importantly, the increased telomerase activity was correlated with a decrease in levels of depression and increase in mental health score when both groups are combined. This suggests that stress reduction by meditation is accompanied by an increase in telomerase activity.

So far, all three studies I talked about in this blog showed an increased telomerase activity with lifestyle change. However, recent studies have also shown that the relationship between telomerase activity and disease risk factors maybe U-shaped where both low and high telomerase activity are associated with risk factors. Specifically, the combination of high telomerase activity and short telomere length is associated with low socioeconomic status, clinical depression (MDD) and coronary artery calcification.

Initial research on telomeres and stress reduction techniques seems be consistent with other research that points to the health benefits of stress reduction techniques such as improved mood, sleep and immune function. The above studies are compelling in that they suggest that telomere preservation and maintenance is a significant mechanism that results in the positive physical and psychological outcomes associated with meditation and stress reduction measures.

 

 

Jue Lin, PhD

Dr. Lin is a Research Biochemist in the Department of Biochemistry and Biophysics at UCSF and a co-founder of Telomere Diagnostics. She did her postdoctoral work with Dr. Elizabeth Blackburn, a Nobel Laureate in telomere research, investigating telomerase function and regulation.

Read more about Dr. Lin at www.teloyears.com