Elsevier

The Lancet Oncology

Volume 14, Issue 11, October 2013, Pages 1112-1120
The Lancet Oncology

Articles
Effect 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

https://doi.org/10.1016/S1470-2045(13)70366-8Get rights and content

Summary

Background

Telomere shortness in human beings is a prognostic marker of ageing, disease, and premature morbidity. We previously found an association between 3 months of comprehensive lifestyle changes and increased telomerase activity in human immune-system cells. We followed up participants to investigate long-term effects.

Methods

This follow-up study compared ten men and 25 external controls who had biopsy-proven low-risk prostate cancer and had chosen to undergo active surveillance. Eligible participants were enrolled between 2003 and 2007 from previous studies and selected according to the same criteria. Men in the intervention group followed a programme of comprehensive lifestyle changes (diet, activity, stress management, and social support), and the men in the control group underwent active surveillance alone. We took blood samples at 5 years and compared relative telomere length and telomerase enzymatic activity per viable cell with those at baseline, and assessed their relation to the degree of lifestyle changes.

Findings

Relative telomere length increased from baseline by a median of 0·06 telomere to single-copy gene ratio (T/S)units (IQR–0·05 to 0·11) in the lifestyle intervention group, but decreased in the control group (−0·03 T/S units, −0·05 to 0·03, difference p=0·03). When data from the two groups were combined, adherence to lifestyle changes was significantly associated with relative telomere length after adjustment for age and the length of follow-up (for each percentage point increase in lifestyle adherence score, T/S units increased by 0·07, 95% CI 0·02–0·12, p=0·005). At 5 years, telomerase activity had decreased from baseline by 0·25 (–2·25 to 2·23) units in the lifestyle intervention group, and by 1·08 (–3·25 to 1·86) units in the control group (p=0·64), and was not associated with adherence to lifestyle changes (relative risk 0·93, 95% CI 0·72–1·20, p=0·57).

Interpretation

Our comprehensive lifestyle intervention was associated with increases in relative telomere length after 5 years of follow-up, compared with controls, in this small pilot study. Larger randomised controlled trials are warranted to confirm this finding.

Funding

US Department of Defense, NIH/NCI, Furlotti Family Foundation, Bahna Foundation, DeJoria Foundation, Walton Family Foundation, Resnick Foundation, Greenbaum Foundation, Natwin Foundation, Safeway Foundation, Prostate Cancer Foundation.

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.

Section snippets

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

References (50)

  • TL Jacobs et al.

    Intensive meditation training, immune cell telomerase activity, and psychological mediators

    Psychoneuroendocrinology

    (2011)
  • EA Hoge et al.

    Loving-kindness meditation practice associated with longer telomeres in women

    Brain Behav Immun

    (2013)
  • L Paul

    Diet, nutrition and telomere length

    J Nutr Biochem

    (2011)
  • Q Xu et al.

    Multivitamin use and telomere length in women

    Am J Clin Nutr

    (2009)
  • J Daubenmier et al.

    Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study

    Psychoneuroendocrinology

    (2012)
  • JK Kiecolt-Glaser et al.

    Omega-3 fatty acids, oxidative stress, and leukocyte telomere length

    Brain Behav Immun

    (2013)
  • EH Blackburn

    Telomeres and telomerase: the means to the end (Nobel lecture)

    Angew Chem Int Ed Engl

    (2010)
  • MA Shammas

    Telomeres, lifestyle, cancer and aging

    Curr Opin Clin Nutr Metab Care

    (2011)
  • DM Shcherbakova et al.

    Telomerase: structure and properties of the enzyme, characteristics of the yeast telomerase

    Mol Biol (Moscow)

    (2006)
  • M Bisoffi et al.

    Telomeres: prognostic markers for solid tumors

    Int J Cancer

    (2006)
  • J Krauss et al.

    Physical fitness and telomere length in patients with coronary heart disease: findings from the Heart and Soul Study

    PLoS One

    (2011)
  • I Spyridopoulos et al.

    Accelerated telomere shortening in leukocyte subpopulations of patients with coronary heart disease: role of cytomegalovirus seropositivity

    Circulation

    (2009)
  • V Codd et al.

    Identification of seven loci affecting mean telomere length and their association with disease

    Nat Genet

    (2013)
  • AK Meeker et al.

    Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis

    Cancer Res

    (2002)
  • CM Heaphy et al.

    Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death

    Cancer Discov

    (2013)
  • Cited by (292)

    • Biomarkers in adult spinal deformity surgery

      2023, Seminars in Spine Surgery
    View all citing articles on Scopus
    View full text