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: 10671527
• 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/10671527
• 关键词: Acceleration; Accounting; Activities of Daily Living; Adult; Age; Aging; Behavior Therapy; Bioinformatics; Biological; Biological Markers; Blood; Board Certification; Bone Marrow; Cell division; Cells; 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; cancer therapy; 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.

超过60%的髓系肿瘤(MN)是在60岁的成年人中被诊断出来的，而高达73%的老年患者被诊断为≥ MN患者在化疗前和化疗中均有功能损害。建立生物标记物以识别 有功能衰退风险的老年MN患者，了解功能衰退的机制可以指导 预防功能衰退的干预措施。DNA甲基化(DNaM)AGE，一种新的、有前途的生物标志物 生物学年龄，可以用来识别有功能衰退风险的老年患者。DNaM年龄捕获 其他信息，如暴露和其他应激源，使其更好地反映生物年龄 与实际年龄相比。加速dNaM年龄(dNaM年龄减去时间顺序年龄)与 在普通人群中具有功能衰退、虚弱、发病率和死亡率。癌症风险与以下因素有关 加速的dNaM年龄和化疗导致化疗前和化疗后dNaM的深刻变化 在患有癌症的老年人中。文献表明，dNaM年龄可能是一个更好的风险指标 年龄较大的MN患者的功能衰退。DNaM受锻炼的影响 随着时间的推移减缓dNaM年龄增长的速度；运动也是一种有希望的干预措施，以防止功能性 老年MN患者下降。然而，目前还不知道运动是否可以减缓dNaM的速度。 癌症患者的年龄增加或逆转。了解运动性表观遗传学 老年MN患者是高危人群，其变化具有重要的临床意义。这位候选人是Dr。 陆家宝，拥有内科、血液学、肿瘤学和老年病学方面的董事会认证。作为她NCI的一部分 K99/R00，陆恭蕙博士发起了一项试点随机对照试验(RCT)，以评估 运动干预与控制对老年MN门诊患者功能状态的影响 化疗超过12周。GEMSSTAR R03将允许陆博士利用这项独特的研究 调查1)调查外周血dNaM年龄加速与功能衰退的关系 在患有MN的老年人中，2)探索运动诱导的MN老年患者的表观遗传学变化，以及3) 探讨外周血与骨髓dNaM年龄的相关性。R03将补充Dr。 LOH的K99/R00，使她能够研究dNaM年龄作为功能衰退的新生物标志物以及 对患有癌症的老年人进行dNaM锻炼。此外，陆恭蕙博士将可扩展她在 表观遗传学、生物信息学和癌症和衰老方面的翻译研究 指导团队。陆恭蕙博士的R03和K99/R00将共同为第三阶段随机对照试验提供初步数据 评估mHealth运动干预对功能衰退和表观遗传学标记物的影响。这个 培训和研究相结合的计划也将使陆博士成为为数不多的老年肿瘤学之一 研究移动健康行为干预以及这些干预机制的研究人员 改善老年MN患者的预后。