DataSheet_1_Associations between exercise capacity, p16INK4a expression and inflammation among adult survivors of childhood cancer.pdf

BackgroundOver 50% of childhood cancer survivors are exercise intolerant, with maximal aerobic capacities comparable to individuals decades older, suggesting early physiologic ageing. In addition, 36% of survivors are obese. Optimal exercise capacity provides a foundation to support daily function and healthy body habitus and is associated with benefits to cognition, cardiovascular health, and longevity. Cellular senescence and inflammation are key mechanisms that drive age-related disease, quantifiable as biomarkers in peripheral blood.AimsThis study aimed to evaluate associations between p16INKa, a biomarker of cellular senescence, and inflammation and exercise capacity among adult survivors of childhood cancer.Materials and methodsEligible survivors were recruited from the St. Jude Lifetime (SJLIFE) Cohort Study. Exercise capacity was assessed by maximal oxygen uptake (VO2, ml/kg/min) obtained via cardiopulmonary exercise testing using a modified Bruce protocol. Body fat (%) was determined from dual energy x-ray absorptiometry (DEXA). Peripheral blood samples were used to evaluate log2 p16INK4a mRNA expression, a biomarker of cellular senescence, and inflammation with high sensitivity C-reactive protein (hs-CRP) levels. Multivariable regression evaluated associations between p16INK4a, hs-CRP, body fat, and exercise capacity.ResultsParticipants included 185 five-year childhood cancer survivors (mean age 36.6 [range 20.1 - 55.7] years, 44% male, 77% non-Hispanic white, 53% leukemia/lymphoma). Compared to males, females had lower peak VO2 (mean ± SD, 22.5 ± 8.2 vs. 28.8 ± 7.7 ml/kg/min, p

背景：超过50%的儿童癌症幸存者对运动耐受力不足，其最大摄氧量与数十岁的人群相当，这表明早期生理性衰老。此外，36%的幸存者肥胖。理想的运动能力为支持日常功能与健康的体态奠定基础，并与认知、心血管健康和长寿的益处相关。细胞衰老和炎症是驱动与年龄相关疾病的两种关键机制，这些机制可以通过外周血液中的生物标志物进行量化。目标：本研究旨在评估细胞衰老生物标志物p16INKa与炎症及运动能力之间在成年儿童癌症幸存者中的关联。材料与方法：合格的幸存者来自圣犹达终身（SJLIFE）队列研究。运动能力通过改良布鲁斯方案进行的心肺运动测试所获得的最高摄氧量（VO2，ml/kg/min）进行评估。身体脂肪百分比通过双能X射线吸收测定法（DEXA）确定。外周血样本用于评估细胞衰老生物标志物p16INK4a mRNA表达的log2值，以及通过高敏C反应蛋白（hs-CRP）水平评估炎症。多变量回归评估了p16INK4a、hs-CRP、身体脂肪与运动能力之间的关联。结果：参与者包括185名五岁儿童癌症幸存者（平均年龄36.6岁[范围20.1 - 55.7岁]，44%为男性，77%为非西班牙裔白人，53%为白血病/淋巴瘤）。与男性相比，女性的峰值摄氧量较低（平均±标准差，22.5±8.2 vs. 28.8±7.7 ml/kg/min，p