Nong Jingying, Wang Yu, Zhang Yi
Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Changchun Street 45#, Beijing, 100053, China.
Center for Applied Statistics and School of Statistics, Renmin University of China, Zhongguancun Street 59#, Beijing, 100872, China.
Clin Epigenetics. 2025 Jun 16;17(1):103. doi: 10.1186/s13148-025-01912-1.
Cancer remains a serious public health problem impeding gains in life expectancy. Epigenetic clocks, derived from sets of DNA methylation CpGs and mathematical algorithms, have demonstrated a remarkable ability to indicate biological aging and age-related health risks. Dunedin(P)ace(o)f(A)ging(m)ethylation is a single-timepoint DNA methylation clock. It is an aging speedometer rather than a state measure. The association between the DunedinPoAm-measured pace of biological aging and cancer risk based on a nationally non-institutionalized sample remains to be elucidated. Physical activity, a modifiable lifestyle factor, is associated with delayed biological aging and lower risks of developing cancer. We hypothesized that DunedinPoAm-measured pace of biological aging is positively associated with cancer risk, and physical activity moderates this association.
In total, 2,529 participants aged 50 or older from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 were included. Weighted logistic regression calculating odds ratios (OR) and 95% confidence intervals (CI) showed that when scaled per 1-SD increase, DunedinPoAm was positively associated with cancer risk (OR, 95% CI) (1.21, 1.05-1.39) in the crude model and adjusted for age and sex (1.19, 1.01-1.40). Individuals of high DunedinPoAm tertile had a 68% (95% CI 1.16-2.43) increase in cancer risk compared with the low tertile (P trend < 0.001). As hypothesized, effect modification by physical activity was significant (P interaction = 0.013). The association was apparent in physically inactive participants (1.52, 1.16-2.00), whereas insignificant in physically active individuals (1.08, 0.89-1.32). Exploratory interaction analyses for other covariates showed significant effect modification by age (> 65 years, 1.38, 1.08-1.77 vs 50-65 years, 1.00, 0.79-1.27).
The study supported the hypothesis by demonstrating a positive association between the DunedinPoAm-measured pace of biological aging and cancer risk and a modulating role of physical activity. Physically inactive individuals or participants over 65 years showed increased susceptibility to this association. These findings suggest that incorporating the DunedinPoAm-measured pace of biological aging into cancer screening strategies may benefit those with physically inactive lifestyles and older individuals. Whether physical activity can mitigate the increased risk of cancer in individuals with a faster pace of biological aging needs to be validated in further interventional cohort studies.
癌症仍然是一个严重的公共卫生问题，阻碍了预期寿命的提高。表观遗传时钟源自一组DNA甲基化CpG和数学算法，已显示出显著的能力来指示生物衰老和与年龄相关的健康风险。达尼丁（P）衰老（o）速度（A）甲基化是一种单时间点DNA甲基化时钟。它是一个衰老速度计而非状态度量。基于全国非机构化样本，达尼丁多胺测量的生物衰老速度与癌症风险之间的关联仍有待阐明。身体活动是一个可改变的生活方式因素，与生物衰老延迟和患癌风险降低相关。我们假设，达尼丁多胺测量的生物衰老速度与癌症风险呈正相关，且身体活动可调节这种关联。
总共纳入了1999 - 2002年国家健康与营养检查调查（NHANES）中2529名50岁及以上的参与者。加权逻辑回归计算比值比（OR）和95%置信区间（CI）显示，在未调整模型中，每增加1个标准差进行标度时，达尼丁多胺与癌症风险呈正相关（OR，95% CI）（1.21，1.05 - 1.39），在调整年龄和性别后（1.19，1.01 - 1.40）。与低三分位数相比，达尼丁多胺三分位数高的个体患癌风险增加68%（95% CI 1.16 - 2.43）（P趋势＜0.001）。如所假设的，身体活动的效应修正显著（P交互作用 = 0.013）。这种关联在身体不活动的参与者中明显（1.52，1.16 - 2.00），而在身体活动的个体中不显著（1.08，0.89 - 1.32）。对其他协变量的探索性交互分析显示，年龄的效应修正显著（＞65岁，1.38，1.08 - 1.77 vs 50 - 65岁，1.00，0.79 - 1.27）。
该研究通过证明达尼丁多胺测量的生物衰老速度与癌症风险之间的正相关以及身体活动的调节作用，支持了这一假设。身体不活动的个体或65岁以上的参与者对这种关联的易感性增加。这些发现表明，将达尼丁多胺测量的生物衰老速度纳入癌症筛查策略可能有益于那些身体不活动的生活方式者和老年人。身体活动是否能减轻生物衰老速度较快个体患癌风险增加的问题，需要在进一步的干预队列研究中得到验证。
