Indicators of Accelerated Aging in Asian American Childhood Survivors

亚裔美国童年幸存者加速衰老的指标

• 批准号: 10910604
• 负责人: Joel E Milam
• 金额: $ 19.99万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10910604
• 关键词: Acceleration; Address; Adult; Affect; Age; Age Years; Aging; American; Area; Asia; Asian; Asian Americans; Asian population; Attention; Behavior; Biological Aging; Biological Markers; Body Composition; Body fat; Body mass index; Brain-Derived Neurotrophic Factor; California; Cardiovascular Diseases; Caucasians; Central Nervous System; Childhood; Childhood Cancer Survivor Study; Chronic; Cohort Studies; Combined Modality Therapy; Comparative Study; County; DNA Methylation; Data; Diagnosis; Dyslipidemias; East Asian; Elderly; Eligibility Determination; Ethnic Origin; European; Friends; Genetic Predisposition to Disease; Health; Hematopoietic Stem Cell Transplantation; Inflammation; Inflammatory; Intake; Intelligence; Interleukin-6; Intervention; Late Effects; Lead; Length; Life Style; Literature; Long-Term Effects; Los Angeles; Malignant Childhood Neoplasm; Malignant Neoplasms; Malignant neoplasm of brain; Measurement; Measures; Memory; Mental Health; Metabolic; Metabolic syndrome; Methotrexate; Mitochondrial DNA; Modality; Neurocognitive; Neurocognitive Deficit; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Nutritional; Operative Surgical Procedures; Oranges; Oxidative Stress; Parents; Participant; Patients; Phenotype; Physical activity; Plasma; Population; Population Heterogeneity; Population Study; Predisposition; Premature Mortality; Premature aging syndrome; Prevention; Race; Radiation therapy; Regimen; Research; Risk; SEER Program; Sampling; Siblings; Socioeconomic Status; Spouses; Survivors; Symptoms; Systemic disease; TNF gene; Telomere Shortening; Treatment Protocols; Treatment-Related Cancer; Treatment-related toxicity; Variant; cancer type; chemotherapy; childhood cancer survivor; circulating biomarkers; clinical biomarkers; cognitive function; cognitive performance; comparison control; cytokine; ethnic diversity; executive function; experience; frailty; high risk; insight; irradiation; lean body mass; muscle form; national surveillance; neoplasm registry; neurotoxic; population based; premature; prevent; processing speed; racial difference; racial diversity; recruit; telomere; tool; treatment effect

Abstract With treatment advances for childhood cancer, over 80% of patients achieve long-term survival. To achieve cure, childhood cancer survivors (CCS) undergo intensive, multimodal treatment regimens including combinations of surgery, chemotherapy, radiation therapy, and hematopoietic stem cell transplantation. Such regimens put these patients at risk of adverse late health effects including cardiovascular disease, neurocognitive problems, endocrinopathies, mental health issues, and premature mortality. An important mechanism which may increase the risk of late effects in CCS is premature biological aging. A substantial percent of CCS experience frailty, a phenotype commonly studied in older adults which is characterized by reduction in at least three physical ability measurements. CCS also suffer from cancer-related neurocognitive impairment, which has been found in approximately 35% of CCS and includes declines in intelligence, attention, memory, processing speed, and executive function. Other markers of accelerated aging that have been identified in CCS include chronic inflammation and metabolic syndrome leading to abnormal body fat distribution, decreased proportion of lean body mass, and dyslipidemia symptoms. Missing from this research is the examination of markers of accelerated aging among racial and ethnic CCS groups other than non- Hispanic whites, as the majority of studies in this area have been limited to Caucasian populations. Studies set among older adults have shown variability in aging by race and ethnicity. Among East Asians, specific mitochondrial DNA variation has been identified that predisposes Asians to type 2 diabetes despite having lower mean body mass index than European populations. In comparative studies focused on CCS set in Asia, Asian CCS demonstrated worse treatment-related neurocognitive impairment compared to non-Hispanic whites and possess specific genetic susceptibilities for treatment-related toxicities such as neuropathy. Despite potential unique differences by race/ethnicity in accelerated aging in CCS, little research has been conducted in diverse populations. To address this research gap, we propose in this supplement to examine indicators of accelerated aging among Asian American CCS participating in a population-based R01 (1R01CA261888-01) compared to race- and age-matched controls. Our aims are: Aim 1: To assess cognitive performance in Asian American CCS compared to controls. Aim 2: To measure circulating biomarkers related to aging in Asian American CCS compared to controls. Aim 3: To assess changes in body-composition related to metabolic- aging in Asian American CCS compared to controls. The proposed research will provide important preliminary data to assess the potentially unique impacts of cancer-related treatment on accelerated aging among Asian American CCS. Such research may enable tailored surveillance and interventions to prevent late effects to which Asian American CCS may be uniquely susceptible.

抽象的 随着儿童癌症治疗的进步，超过 80% 的患者实现了长期生存。达到 治愈，儿童癌症幸存者（CCS）接受强化、多模式治疗方案，包括 手术、化疗、放射治疗和造血干细胞移植的组合。这样的 治疗方案使这些患者面临后期健康不良影响的风险，包括心血管疾病、 神经认知问题、内分泌疾病、心理健康问题和过早死亡。一个重要的 可能增加 CCS 迟发效应风险的机制是过早的生物衰老。一个实质性的 百分比的 CCS 经历虚弱，这是老年人中常见的一种表型，其特征是 至少三项身体能力测量值降低。 CCS 还患有癌症相关的神经认知疾病 约 35% 的 CCS 中发现了损害，包括智力下降， 注意力、记忆力、处理速度和执行功能。其他加速衰老的标志 CCS 中已发现包括慢性炎症和代谢综合征，导致身体脂肪异常 分布、去脂体重比例下降和血脂异常症状。本研究中缺失 是对非非非居民以外的种族和族裔 CCS 群体中加速衰老标志物的检查 西班牙裔白人，因为该领域的大多数研究仅限于白种人群体。研究集 老年人中的老龄化表现出种族和民族的差异。在东亚人中，具体 尽管亚洲人患有 2 型糖尿病，但线粒体 DNA 变异已被确定为易患 平均体重指数低于欧洲人口。在针对亚洲 CCS 的比较研究中， 与非西班牙裔相比，亚洲 CCS 表现出更严重的治疗相关神经认知障碍 白人对神经病等治疗相关毒性具有特定的遗传易感性。尽管 种族/族裔在 CCS 加速衰老方面存在潜在的独特差异，但很少有研究进行 在不同的人群中。为了弥补这一研究空白，我们在本补充文件中建议检查以下指标： 参与基于人口的 R01 的亚裔美国人 CCS 加速老龄化 (1R01CA261888-01) 与种族和年龄匹配的对照相比。我们的目标是： 目标 1：评估亚洲人的认知表现 美国 CCS 与对照相比。目标 2：测量亚洲人与衰老相关的循环生物标志物 美国 CCS 与对照相比。目标 3：评估与代谢相关的身体成分变化 与对照组相比，亚裔美国人 CCS 的衰老情况。拟议的研究将提供重要的初步 用于评估癌症相关治疗对亚洲人加速衰老的潜在独特影响的数据 美国CCS。此类研究可以实现有针对性的监测和干预，以防止后期影响 亚裔美国人 CCS 可能特别容易受到影响。