唧唧堂编辑二朵2013-12-26 11:42 PM

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 综合生活方式的改善对活检证实患有低危前列腺癌的男性的端粒酶活性和端粒长度的影响:5年随访的描述性试验研究

Abstract 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. 背景 在人类中端粒长度缩短是年龄增长、疾病发生和过早发病的预测因素。我们既往已经在人类免疫系统细胞中发现,3个月时间综合生活方式的改变和端粒活性增加之间存在一定的联系。在本文中,我们对受测参与者进行了跟踪随访来调查这种联系的长期效应。 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. 方法 随后的这项随访研究比较了10名男性和25名已经活检证实为低危前列腺癌的患者作为外部对照,这些患者都选择了采取积极随访的治疗方案。研究者根据以往相同的入组标准从既往的研究中选择了2003年至2007年符合标准规定的受试者。干预组的男性患者按规定进行了综合生活方式的变化(包括饮食、运动、压力处理和社会支持等方面的改变),而在对照组的男性患者则仅接受密切的随访监测。在第5年时,我们对受试者进行血样采集,比较了每个存活细胞的端粒长度和端粒酶活性与入组时相比的变化情况,并且根据(受试者)生活方式的变化程度评价鉴定了其与端粒各方面变化之间所可能存在的联系。 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). 发现 与入组时相比,生活方式干预组的受试者的每个拷贝基因比率(T/S)单位的中位变化值为0.06(IQR –0·05 to 0·11),而在对照组T/S则出现降低(–0·03 T/S units, –0·05 to 0·03, difference p=0·03)。当研究者将两组的数据进行整合时,在调整了年龄和随访时间等因素之后,研究者发现生活方式的改变与端粒相对长度具有显著相关性(生活方式依从性得分每增加一个百分点,则拷贝基因比率(T/S)单元随之上升0.07,95%置信区间为0·02至0·12, p=0·005)。在第5年时,在生活方式干预组中,与入组时相比,端粒的活性降低了0.25单位(–2·25 至 2·23),而在对照组中降低了1.08单位(–3·25 to 1·86),并且这种端粒活性的降低与生活方式的改变不存在显著相关性(相关风险为0.93,95%置信区间为0.72至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. 说明 在随后持续5年的随访后,我们发现与对照组相比,该小规模试点研究实验中综合生活方式的干预变化与相对端粒长度增加具有相关性,但仍需要大型的随机对照研究来进一步确证本研究的结果。 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.

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