Exercise slows biological aging in breast cancer survivors: secondary analysis of a randomized trial.

IF 7.7 1区 医学 Q1 ONCOLOGY
Daniel Carlin, Olivia Ott, Dorothy D Sears, Tim Ahles, Paula Desplats, Sheri J Hartman
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Abstract

Background: Cancer and its treatments are associated with accelerated biological aging and cognitive impairment among breast cancer survivors. DNA methylation-based epigenetic clocks provide measures of biological aging that predict morbidity and mortality, yet little is known about whether these aging trajectories can be modified by lifestyle intervention. This secondary analysis of a subset of participants in a randomized controlled trial examined the impact of a 12-month exercise intervention on markers of epigenetic aging among breast cancer survivors.

Methods: Sedentary breast cancer survivors within 5 years of diagnosis were randomized to a remotely delivered exercise intervention or a contact-matched health & wellness condition. Whole blood samples and cognitive assessments were obtained at baseline, 6, and 12 months. Epigenetic ages and differential methylation were calculated from normalized data obtained from the Methylation Screening Array.

Results: A subsample of 124 participants with complete data was analyzed. The Exercise arm showed slower epigenetic aging than the Health & Wellness arm over the 12-month study, according to GrimAge2 (P = .02) and DNAmFitAge (P = .002) clocks. Changes in epigenetic aging were significantly correlated with alterations in attention and self-reported cognition, with faster epigenetic aging associated with greater cognitive decline. Furthermore, genome-wide analysis of the blood epigenome identified differentially methylated sites, some mapping to genes enriched for BDNF (brain-derived neurotrophic factor) signaling pathways.

Conclusion: A 12-month exercise intervention was associated with slower epigenetic aging among breast cancer survivors. These findings suggest that biological aging may represent a modifiable mechanism through which exercise supports cognitive health in cancer survivorship.

Trial registration: ClinicalTrials.gov Identifier: NCT04049695.

运动减缓乳腺癌幸存者的生物衰老:随机试验的二次分析。
背景:癌症及其治疗与乳腺癌幸存者的加速生物衰老和认知障碍有关。基于DNA甲基化的表观遗传时钟提供了预测发病率和死亡率的生物衰老测量方法,但人们对这些衰老轨迹是否可以通过生活方式干预来改变知之甚少。这项对一组随机对照试验参与者的二次分析研究了12个月的运动干预对乳腺癌幸存者表观遗传衰老标志物的影响。方法:确诊5年内久坐不动的乳腺癌幸存者被随机分配到远程提供的运动干预组或接触者匹配的健康状况组。在基线、6个月和12个月时获得全血样本和认知能力评估。表观遗传年龄和差异甲基化是根据甲基化筛选阵列获得的归一化数据计算的。结果:对数据完整的124名参与者进行了子样本分析。根据GrimAge2 (P = .02)和DNAmFitAge (P = .002)时钟,在12个月的研究中,运动组的表观遗传衰老速度比健康与保健组慢。表观遗传衰老的变化与注意力和自我报告的认知能力的改变显著相关,更快的表观遗传衰老与更大的认知能力下降相关。此外,血液表观基因组的全基因组分析鉴定了差异甲基化位点,其中一些定位于BDNF(脑源性神经营养因子)信号通路富集的基因。结论:在乳腺癌幸存者中,12个月的运动干预与减缓表观遗传衰老有关。这些发现表明,生物衰老可能代表了一种可改变的机制,通过这种机制,运动支持癌症幸存者的认知健康。试验注册:ClinicalTrials.gov标识符:NCT04049695。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
17.00
自引率
2.90%
发文量
203
审稿时长
4-8 weeks
期刊介绍: The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.
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