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

Published in The Lancet Oncology

Authors: Ornish D, Lin J, Chan JM, Epel E, Kemp C, Weidner G, Marlin R, Frenda SJ, Magbanua MJ, Daubenmier J, Estay I, Hills NK, Chainani-Wu N, Carroll PR, Blackburn EH,

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 10 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 under- went 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 sin- gle-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).

Interpretations: 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 randomized controlled trials are warranted to confirm this finding.

Key Takeaways:

• Comprehensive lifestyle changes, as defined by the Ornish program, were found to significantly increase telomere length over 5-years compared to a control group
• Telomere length is a molecular marker of aging; telomere shortening is associated with increased disease risk, including cardiovascular disease and cancer, and premature death
• Greater adherence to lifestyle changes were significantly associated with greater telomere length
• Overall, the Ornish comprehensive lifestyle intervention can decrease the aging process at the
  cellular level