Healthy Habits Linked to Longer Telomeres in Prostate Cancer

Neil Osterweil

September 16, 2013

A comprehensive lifestyle intervention might help prostate cancer patients live to be longer in the tooth and in the telomere, suggest results of a very small pilot study reported online in The Lancet Oncology.

Among 35 men with biopsy-proven, low-risk prostate cancer who opted for active surveillance, a comprehensive lifestyle intervention including diet, activity, stress management, and support was associated with lengthening of telomeres over 5 years compared with a loss of telomere length among controls, report Dean Ornish MD, director of the Preventive Medicine Research Institute, in Sausalito, California, and colleagues.

Telomeres, complexes of DNA and proteins at the end of linear chromosomes, have been shown to be essential for cellular health. Telomere shortening has been associated with increased risk for prostate cancer recurrence in patients who have undergone radical prostatectomy, and it's theorized that telomere maintenance and lengthening may be associated with better health and longer life.

"This study is the first controlled study to show that any intervention may lengthen telomeres in humans, but it's not in a vacuum," Dr. Ornish said in an interview with Medscape Medical News. "There are other, cross-sectional studies showing that people who are under chronic emotional stress tend to have shorter telomeres in direct proportion to the amount of stress they have, or that people who are marathon runners tend to have longer telomeres than those who aren't."

The active intervention group included 10 men who were participants in the GEMINAL (Gene Expression Modulation by Intervention with Nutrition and Lifestyle) study. The participants ate a diet low in fat and refined carbohydrates and high in whole fruits and vegetables; exercised aerobically for at least 30 minutes 6 days each week; engaged in stress management programs; and took part in a 1-hour weekly support group. Controls were followed with active surveillance only.

The investigators looked at telomere length in peripheral blood mononuclear cells, measured as the length of telomeres relative to standard reference DNA. The measure is expressed as a telomere to single-copy gene ratio (T/S).

Over 5 years, men in the lifestyle intervention group had an increase in relative telomere length over baseline of a median 0.06 T/S (interquartile range [IQR], -0.05 to 0.11). In contrast, controls had telomere shortening, by a median of -0.03 T/S (IQR, -0.05 to 0.03), and this difference was significant ( P = .03).

A bivariate analysis of combined intervention and control-group data adjusted for age and length of follow-up also showed an association between lifestyle changes and telomere length, with each percentage-point increase in adherence to lifestyle changes translating into a 0.07 increase in T/S (P = .005).

"Our findings are biologically plausible and consistent with earlier studies. Nevertheless, in view of the small sample size and this being a pilot study, we report increases as associations without necessarily proving causation. Additionally, although increases in relative telomere length are thought to be beneficial, the full biological implications remain to be determined in large randomized, controlled trials," Dr. Ornish and colleagues write.

Encouraging Results

"I think that it's really encouraging that an intervention study of this type, which is by nature going to have a small sample size, could show these differences in telomere length," said Timothy Rebbeck, PhD, professor of epidemiology at Perelman School of Medicine at the University of Pennsylvania, in Philadelphia.

Dr. Rebbeck, who was not involved in the study, notes that determining the mechanism of the effect may be very difficult, because the biology of telomere length maintenance and shortening is highly complex, involving the telomerase enzyme and multiple proteins in various combinations.

"It's well known that stress, smoking, and various kinds of unfavorable environments cause telomeres to shorten, and we really don't know exactly what that is all about," he said.

He also commented that investigators would be wise going forward to employ other methods for measuring telomere length and function in addition to the T/S ratio used in the study.

"The T/S ratio is sort of an overall measure of telomere length, but there might be individual telomeres on individual chromosomes that might be shortening or lengthening, and narrowing that mechanism down might help us understand better what is happening," Dr, Rebbeck said.

Dr. Ornish saidthat his group hopes to follow the men over time to see whether there is a correlation between telomere length and disease progression.

The study was funded by the US Department of Defense, the National Cancer Institute, Furlotti Family Foundation, Bahna Foundation, DeJoria Foundation, Walton Family Foundation, Resnick Foundation, Greenbaum Foundation, Natwin Foundation, Safeway Foundation, and Prostate Cancer Foundation. Coauthors Jue Lin, Elissa Epel, and Elizabeth H. Blackburn were cofounders of Telome Health, Inc, a diagnostic company that assesses telomere biology. Dr. Rebbeck has disclosed no relevant financial relationships.

Lancet Oncol. Published online September 16, 2013. Abstract

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