Epigenetic markers, functional status, and exercise in older adults with myeloid neoplasms

患有髓系肿瘤的老年人的表观遗传标记、功能状态和运动

• 批准号: 10517787
• 负责人: Kah Poh Loh
• 金额: $ 15.4万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10517787
• 关键词: Acceleration; Accounting; Activities of Daily Living; Adult; Age; Aging; Behavior Therapy; Bioinformatics; Biological; Biological Markers; Blood; Bone Marrow; Cell division; Cells; Chemotherapy-Oncologic Procedure; Chronology; Complement; Control Groups; DNA Methylation; DNA analysis; Data; Diagnosis; Drops; Elderly; Epigenetic Process; Exercise; General Population; Geriatrics; Grant; Hematology; Individual; Inherited; Internal Medicine; Interruption; Intervention; Literature; Malignant Neoplasms; Measures; Mentors; Methylation; Morbidity - disease rate; Myeloproliferative disease; Oncology; Outpatients; Patient Self-Report; Patients; Peripheral; Phase; Physical Performance; Positioning Attribute; Quality of life; Randomized Controlled Trials; Reporting; Research; Research Personnel; Risk; Sampling; Site; Time; Tissues; Training; Translational Research; aged; cancer risk; chemotherapy; clinically significant; epigenetic marker; exercise intervention; experience; frailty; functional decline; functional disability; functional status; group intervention; high risk population; improved outcome; instrumental activity of daily living; interest; mHealth; mortality; novel; novel marker; older patient; peripheral blood; prevent; prospective; public health relevance; randomized trial; recruit; standard of care; stressor

Over 60% of myeloid neoplasms (MN) are diagnosed in adults aged ≥60 years, and up to 73% of older patients with MN experience functional impairment before and during chemotherapy. Establishing biomarkers to identify older patients with MN at risk for functional decline and understanding the mechanisms of decline could guide interventions to prevent functional decline. DNA methylation (DNAm) age, a novel and promising biomarker of biological age, may be used to identify older patients at risk for functional decline. DNAm age captures additional information such as exposures and other stressors that make it a better reflection of biological age compared to chronological age. Accelerated DNAm age (DNAm age minus chronological age) is associated with functional decline, frailty, morbidity, and mortality in the general population. Cancer risk is associated with accelerated DNAm age and chemotherapy leads to profound DNAm changes from pre- to post-chemotherapy in older adults with cancer. The literature suggests that DNAm age may be a better indicator of risk for functional decline among older patients with MN than chronological age. DNAm is influenced by exercise which slows the rate of DNAm age increase over time; exercise is also a promising intervention to prevent functional decline in older patients with MN. It is not yet known, however, whether exercise can slow the rate of DNAm age increase or reverse DNAm age in patients with cancer. Understanding exercise-induced epigenetic changes in older patients with MN, a high risk population, is of great clinical significance. The candidate, Dr. Kah Poh Loh, is board-certified in internal medicine, hematology, oncology, and geriatrics. As part of her NCI K99/R00, Dr. Loh has initiated a pilot randomized controlled trial (RCT) to assess the preliminary efficacy of an mHealth exercise intervention versus control on functional status in older patients with MN receiving outpatient chemotherapy over 12 weeks. The GEMSSTAR R03 will allow Dr. Loh to leverage this unique study to investigate 1) to investigate the association of accelerated peripheral blood DNAm age with functional decline in older adults with MN, 2) to explore exercise-induced epigenetic changes in older patients with MN, and 3) to explore the correlation between peripheral blood and bone marrow DNAm ages. The R03 will complement Dr. Loh’s K99/R00 by allowing her to study DNAm age as a novel biomarker of functional decline and the effect of exercise on DNAm on older adults with cancer. In addition, Dr. Loh will be able to expand her training in epigenetics, bioinformatics, and translational research in cancer and aging under the guidance of an excellent mentoring team. Together, Dr. Loh’s R03 and K99/R00 will provide preliminary data for a phase 3 RCT evaluating the effects of a mHealth exercise intervention on functional decline and epigenetic markers. The combined training and research plan will also position Dr. Loh to become one of the few geriatric oncology investigators studying mHealth behavioral interventions and the mechanisms by which these interventions improve outcomes in older patients with MN.

在≥60岁的成年人中诊断出超过60％的髓样肿瘤（MN），最多73％ 在化学疗法之前和期间，MN经历了功能障碍。建立生物标志物以识别 MN患有功能下降的风险和了解下降机制的老年患者可以指导 防止功能下降的干预措施。 DNA甲基化（DNAN）年龄，一种新颖而有前途的生物标志物 生物年龄可用于识别有功能下降风险的老年患者。 Dnam Age捕获 其他信息，例如暴露和其他压力源，使其更好地反映生物年龄 与年代年龄相比。加速DNAM年龄（DNAM Age Minus年代年龄）与 一般人群的功能下降，脆弱，发病率和死亡率。癌症风险与 加速DNAM的年龄和化学疗法导致DNAM从化学疗法和化学后的深刻变化 在癌症的老年人中。文献表明，dnam年龄可能是更好的指标 MN患者的功能下降比年代年龄年龄的年龄。 Dnam受运动的影响 随着时间的流逝，DNAM年龄的增长速度降低了；锻炼也是防止功能的承诺干预措施 老年患者的下降。但是，尚不清楚运动是否会减慢DNAM的速度 癌症患者的年龄增加或反向DNAM年龄。了解运动引起的表观遗传学 老年患者（高风险人群）的变化具有极大的临床意义。候选人，博士 KAH POH LOH，在内科，血液学，肿瘤学和老年医学学领域得到认证。作为她的NCI的一部分 LOH博士K99/R00发起了一项试验随机对照试验（RCT），以评估 MHealth锻炼干预与控制MN患者的功能状况的控制 化学疗法超过12周。 Gemsstar R03将使Loh博士能够利用这项独特的研究 调查1）研究加速外周血dnam年龄与功能下降的关联 在具有MN的老年人中，2）探索老年患者运动引起的运动诱导的表观遗传变化，3） 探索外周血和骨髓dnam年龄之间的相关性。 R03将完成Dr. LOH的K99/R00通过允许她研究DNAM时代作为功能下降的新生物标志物和效果 锻炼DNAM对癌症老年人的锻炼。此外，Loh博士将能够扩大她的培训 在优秀的指导下 指导团队。 Loh博士的R03和K99/R00一起将为3阶段RCT提供初步数据 评估MHealth运动干预对功能下降和表观遗传标记的影响。 联合培训和研究计划还将将LOH博士定位为少数几种老年肿瘤学之一 研究MHealth行为干预措施的研究人员以及这些干预措施的机制 改善老年患者的预后。