ArticlesEffect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study
Introduction
Telomeres are protective DNA and protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere maintenance is required for the complete replication of DNA and protection of chromosomes from nuclease degradation, end-to-end fusion, and cellular senescence.1 Telomeres typically shorten during normal cell divisions and, therefore, telomere length and rate of shortening are indicators of mitotic-cell age.2 Telomere shortening is counteracted by the cellular enzyme telomerase.3 In human beings, telomere shortening is a potential prognostic marker for disease risk and progression and for premature death.4
Cellular ageing conferred by diminished telomere maintenance seems to be an important precursor to the development of many types of cancer.5 Shortened telomeres have been associated with poor clinical outcomes, including increased risk of prostate-cancer recurrence after radical prostatectomy.6 Poor outcomes are also reported in patients with coronary heart disease (shortened survival)7 and infectious diseases.8
Short telomere length in peripheral-blood mononuclear cells (PBMCs) is associated with ageing and ageing-related diseases, such as cancer, stroke, vascular dementia, cardiovascular disease, obesity, osteoporosis, and diabetes.1, 9 Telomere attrition has been proposed as a potential mechanism that triggers the chromosomal rearrangement characteristic of prostate cancer.10 Men with variable telomere length in prostate-cancer cells and short telomere length in prostate-cancer-associated stromal cells are at a substantially increased risk of metastasis or dying from prostate cancer.11
In the GEMINAL study12 we investigated the effects of comprehensive lifestyle changes (plant-based diet, moderate exercise, stress management, and increased social support) on telomerase activity in men with low-risk prostate cancer. After 3 months of intervention, telomerase activity was significantly increased in PBMCs. However, although changes in physiological features, such as telomerase activity, can be seen quickly, changes in relative telomere length might not be detectable in such a short period. Therefore, we investigated whether long-term lifestyle changes would affect relative telomere length, telomerase activity, or both, and whether the degree of lifestyle change would alter the extent of the effects.
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Patients
We enrolled all participants between 2003 and 2007. Participants in the intervention group came from the GEMINAL study12 and those in the external control group from the University of California, San Francisco (UCSF) MENS study.13, 14 Eligible participants were men with low-risk prostate cancer who had chosen active surveillance rather than conventional treatment (for reasons unrelated to the study), so it was possible to assess the association between changes in lifestyle and changes in
Results
11 (37%) of the original 30 patients from the lifestyle intervention group had sufficient baseline samples of PBMCs to assess telomerase activity and relative telomere length. However, one patient died after an accident before the end of the study. The lifestyle intervention group, therefore, included ten patients. Of 34 controls enrolled, 25 (74%) had sufficient baseline and available 5-year blood samples for assessment and were included in the analyses. Baseline characteristics of patients
Discussion
After 5 years, relative telomere length had increased in the lifestyle intervention group and decreased in the control group; the difference between the two groups was significant. We also found a correlation between the degree of adherence to the lifestyle changes and the extent of change in relative telomere length. To our knowledge, this is the first time that any intervention has been associated with significant increases in telomere length when compared with a non-intervention group
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