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.

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.