UAB DRC P&F Supplement For Emerging Physician Scientist

项目摘要 在过去的40年里，儿童T2D的严重程度和频率都有所增加，青少年 有T2D经验的人平均预期寿命减少15年。越来越多的证据 提示T2D在青少年中的发生率，其侵袭性的过程，以及对 长寿取决于多种机制，而不是遗传和社会/生活方式决定因素 健康状况有助于解释这一问题。表观遗传学正在成为一种需要考虑的重要机制。之前 研究已经确定了CpG位点的甲基化变化来估计一种细胞类型的总体年龄，以及 与人类长寿有关的表观遗传甲基化模式，称为表观遗传时钟。这个 表观遗传年龄的加速及其与年代年龄的偏离已被证明导致 合并症和全因死亡率增加。关于表观遗传年龄的数据很少，甚至没有。 患有T2D的青少年的加速反应以及表观遗传时钟在T2D患者寿命缩短中的作用 这些病人。 我们将第一次；(1)计算表观遗传年龄并量化表观遗传与表观遗传之间的差异 患有T2D的非裔美国青少年的年龄和实际年龄与BMI、年龄和 性别匹配的青少年，以及(2)调查表观遗传年龄加速的可能机制 在患有T2D的受试者中，通过测试表观遗传年龄和潜在T2D风险因素(即， 体重指数、血糖控制、空腹低密度脂蛋白、甘油三酯、总胆固醇和炎症生物标志物)。我们 假设患有T2D的青少年将比他们的孩子有一个更快的表观遗传年龄 与非糖尿病患者匹配，并且BMI升高，高TG，低HDL值，HbA1C升高，以及 全身性炎症将与表观遗传衰老加速相关。 我们的横断面研究的先导数据将使我们能够为更大规模的表观遗传年龄研究提供信息 作为评估干预效果的生物标志物和更大表观基因组的基础 关联研究以确定可能调节表观遗传年龄的T2D感兴趣基因座 加速。

Project Summary Childhood T2D has increased in severity and frequency over the last four decades, and adolescents with T2D experience on average a reduction in 15 years off of their life expectancy. Mounting evidence suggests that the incidence of T2D in adolescents, its aggressive course, and adverse impact on longevity depends on multiple mechanisms beyond that which genetics and social/lifestyle determinants of health can help explain. Epigenetics is emerging as an important mechanism to consider. Prior studies have identified methylation changes to CpG sites to estimate an overall age of a cell type, and patterns of epigenetic methylation linked to longevity in humans, termed the epigenetic clock. The acceleration of epigenetic age, and its deviation from chronological age, has been shown to lead to increase in comorbidity and all-cause mortality. There is little or no data regarding epigenetic age acceleration in adolescents with T2D and the role of the epigenetic clock in the shortened lifespan of these patients. For the first time, we will; (1) Calculate epigenetic age and quantify the difference between epigenetic age and chronological age in African American adolescents with T2D compared to BMI, age, and gender matched adolescents, and (2) Investigate possible mechanisms for epigenetic age acceleration in subjects with T2D by testing associations between epigenetic age and potential T2D risk factors (i.e., BMI, glycemic control, fasting LDL, TG, total cholesterol, and inflammatory biomarkers). We hypothesize that adolescents with T2D will have an accelerated epigenetic age compared to their matched non-diabetic counterparts, and that elevated BMI, high TG, low HDL, increased HbA1C, and systemic inflammation will be associated with accelerated epigenetic aging. Pilot data from our cross-sectional study would allow us to inform larger studies of epigenetic age as a biomarker for assessing efficacy of interventions and for the basis of larger epigenome-wide association studies to identify loci of interest involved in T2D which may mediate epigenetic age acceleration.