Gerdi Weidner

Increased telomerase activity and comprehensive lifestyle changes: a pilot study.

BACKGROUND Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). METHODS 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. 24 patients had sufficient PBMCs needed for longitudinal analysis. This study is registered on the ClinicalTrials.gov website, number NCT00739791. FINDINGS PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. The increases in telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL) cholesterol (r=-0.36, p=0.041) and decreases in psychological distress (r=-0.35, p=0.047). INTERPRETATION Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Larger randomised controlled trials are warranted to confirm the findings of this study.

Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention.

Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patients 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.

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

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.

Hostility and cardiovascular reactivity to stress in women and men.

&NA; The relationship of Cook Medley hostility scores (Ho) to blood pressure and heart rate reactivity was examined in 56 women and 56 men. Stress was elicited by an unsolvable anagram task that was described as easily solvable. Both men and women scoring high on Ho had greater blood pressure responses to the task. Those scoring high on Ho also reported more anger in response to the tasks, but anger was not associated with blood pressure reactivity. It was concluded that situations evoking suspiciousness and mistrust rather than anger may be necessary to elicit increased blood pressure reactivity among high Ho subjects.

A qualitative analysis of interviews of men with early stage prostate cancer: the Prostate Cancer Lifestyle Trial.

We conducted interviews with a subsample of men (n = 26) participating in the Prostate Cancer Lifestyle Trial (PCLT), who had biopsy-proven prostate cancer (Gleason grade <7; prostate-specific antigen 4–10 ng/mL) and chose “watchful waiting” after diagnosis. The PCLT aimed at improving diet, exercise, stress management practices, and group support within a peer community setting. The aims of this study were to examine psychological, emotional, spiritual, and social reactions to (a) a diagnosis of early stage prostate cancer and (b) participation in the PCLT. Qualitative analyses were completed using MAXqda. Results indicated that the cancer diagnosis was met with anxiety, distress, and denial, or a “bump in the road” attitude. There was some indication that conflict with partners was exacerbated by the diagnosis. A significant component of the lifestyle intervention was involvement in the peer community. This community provided opportunities to experience connections with others facing similar health difficulties. Men generally expressed positive attitudes (emotionally, physically, and spiritually) about the lifestyle change, and felt that their participation in the program contributed to feelings of hope, optimism, and fighting spirit. Additionally, participants frequently mentioned increased comfort with emotional expression.

Sociodemographic diversity and behavioral medicine.

The broad array of economic and cultural diversity in the U.S. population correlates with and impacts on the study of behavioral aspects of health. The purpose of this article was to provide a selective overview of behavioral medicine research on sociodemographically diverse populations, with a focus on ethnicity, gender, and socioeconomic status. Suggestions are provided with regard to methodological refinement of research and insights into possible future directions in behavioral medicine research on ethnically and economically diverse populations.

Effect of intensive lifestyle changes on endothelial function and on inflammatory markers of atherosclerosis.

Intensive lifestyle changes have been shown to regress atherosclerosis, improve cardiovascular risk profiles, and decrease angina pectoris and cardiac events. We evaluated the influence of the Multisite Cardiac Lifestyle Intervention Program, an ongoing health insurance-covered lifestyle intervention conducted at our site, on endothelial function and inflammatory markers of atherosclerosis in this pilot study. Twenty-seven participants with coronary artery disease (CAD) and/or risk factors for CAD (nonsmokers, 14 men; mean age 56 years) were enrolled in the experimental group and asked to make changes in diet (10% calories from fat, plant based), engage in moderate exercise (3 hours/week), and practice stress management (1 hour/day). Twenty historically (age, gender, CAD, and CAD risk factors) matched participants were enrolled in the control group with usual standard of care. At baseline endothelium-dependent brachial artery flow-mediated dilatation (FMD) was performed in the 2 groups. Serum markers of inflammation, endothelial dysfunction, and angiogenesis were performed only in the experimental group. After 12 weeks, FMD had improved in the experimental group from a baseline of 4.23 + or - 0.13 to 4.65 + or - 0.15 mm, whereas in the control group it decreased from 4.62 + or - 0.16 to 4.48 + or - 0.17 mm. Changes were significantly different in favor of the experimental group (p <0.0001). Also, significant decreases occurred in C-reactive protein (from 2.07 + or - 0.57 to 1.6 + or - 0.43 mg/L, p = 0.03) and interleukin-6 (from 2.52 + or - 0.62 to 1.23 + or - 0.3 pg/ml, p = 0.02) after 12 weeks. Significant improvement in FMD, C-reactive protein, and interleukin-6 with intensive lifestyle changes in the experimental group suggests > or = 1 potential mechanism underlying the clinical benefits seen in previous trials.

The effects of academic stress on health behaviors in young adults

Abstract The present study examined changes in health behaviors as a function of academic stress. One-hundred and thirty-three college undergraduate students completed measures of stress, affect, and health-behaviors during times of low and high academic demands. During the high-stress period, negative affect increased and positive affect decreased significantly, while health behaviors deteriorated. The strongest decrements were observed for exercise. Generally, women scored higher on “routine health behaviors” (i.e., self-care, vehicle safety, drug avoidance), but not on behaviors requiring effort (i.e., exercise, healthy nutrition). Distinct patterns of changes in health behaviors and affect were observed: decreases in exercise and self-care were accompanied by decreases in positive affect, whereas decreases in drug avoidance were associated with increases in negative affect. Decreases in the quality of nutrition were linked to both decreases in positive and increases in negative affect. These results s...

Clinical events in prostate cancer lifestyle trial: results from two years of follow-up.

OBJECTIVES Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.

Hostility, social support, and coronary heart disease in the National Heart, Lung, and Blood Institute Family Heart Study

This cross-sectional study investigated the association of hostility and social support to coronary heart disease (CHD) in 2 groups of men and women: those with a familial predisposition for CHD (high-risk sample) and a randomly selected group. The hypothesis was that hostility and low social support would be associated with CHD, and would have a greater effect in the high-risk group. The random sample contained 2,447 individuals (47.1% male) from 576 families, and the high-risk sample consisted of 2,300 people (45.5% male) from 542 families. Odds ratios (OR) and their 95% confidence intervals were calculated using generalized estimating equations (GEE) for logistic regression. Family was specified as the clustering variable, and robust SEEs were obtained to account for dependence of the data within families. After controlling for age, education, body mass index, exercise, smoking history, drinking history, and drinking >5 drinks a day, hostility was associated with a history of coronary bypass surgery or coronary angioplasty in high-risk men (OR 1.21) and a history of myocardial infarction in high-risk women (OR 1.39). High-risk women with high social support had reduced odds of a previous myocardial infarction (OR 0.76), whereas women with high network adequacy in the random sample had reduced risk of myocardial infarction (OR 0.41) and angina (OR 0.49). A ratio of high hostility to low social support was associated with past myocardial infarction in high-risk women (OR 2.47) and a history of angina (OR 2.02) in the random sample men. These results suggest that high hostility and low social support are associated with some manifestations of CHD after controlling for adverse health behaviors.