Social Determinants of Health as Transducers of Cellular Aging: A New Multi-level Paradigm to Reduce Survivorship Disparities at the Intersection of Cancer and Aging

健康的社会决定因素作为细胞衰老的传导者：减少癌症和衰老交叉点的生存差异的新的多层次范式

• 批准号: 10736380
• 负责人: Jeanne Mandelblatt
• 金额: $ 98.04万
• 依托单位: GEORGETOWN UNIVERSITY
• 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 2030-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736380
• 关键词: Acceleration; Advocate; Aging; Animals; Area; Automobile Driving; Award; Black race; Cancer Survivor; Cancer Survivorship; Caring; Cell Aging; Cohort Studies; Collaborations; Complex; Data; Discipline; Disease; Disparity; Environment; Epigenetic Process; Ethnic Origin; Exposure to; Funding; Gene Expression; Geroscience; Goals; Hispanic; Human; Inflammatory; Infrastructure; Institution; Intervention; Knowledge; Laboratories; Lead; Machine Learning; Malignant Neoplasms; Mediation; Methods; Minority; Modeling; Mutation; Oncology; Outcome; Pathway interactions; Policies; Population; Population Sciences; Pre-Clinical Model; Process; Public Health; Quality of life; Race; Research; Research Personnel; Risk; Role; Scientist; Signal Transduction; Stress; Survivors; Testing; Transducers; Translating; United States National Institutes of Health; Vision; cancer care; cancer health disparity; career; clinical care; clinically relevant; cohort; demographics; ethnic minority; health determinants; health disparity; health inequalities; insight; intersectionality; novel; pre-clinical; programs; racial minority; simulation; social health determinants; success; survivorship; transcriptomics; virtual

By 2030, three-quarters of the 22 million US cancer survivors will be 65 and older and the number of older Hispanic and Black survivors will have grown three times faster than Whites. These shifting demographics are driving a crisis in cancer care due to a paucity of evidence to guide care for older survivors, especially older racial/ethnic survivors for whom data is virtually lacking. Filling these gaps will require an understanding of several complex multidirectional relationships at the intersection of health disparities, aging and cancer. Compared to older White survivors, older racial/ethnic minority survivors have had more lifetime exposures to adverse social determinants of health. These exposures accelerate aging processes. Aging increases the risk of developing cancer through accumulated damage and mutations. Cancer and its therapies, in turn, are disease drivers of aging. Together, these intersecting forces are likely to exacerbate current racial/ethnic cancer disparities in the health and quality of life of older survivors. The vision for this Outstanding Investigator Award is to fundamentally shift how we approach cancer disparities by providing a mechanistic understanding of the role of cellular aging in the relationships between social determinants of health and survivorship outcomes. I will use a conceptual model that integrates a multi-level disparities framework with oncology and geroscience perspectives to conduct research using transcriptomic and other -omics analyses, epigenetics, machine learning, mediation models, meta-synthesis and population simulation methods. The broad goals of my transdisciplinary research program are to: 1) discover cellular aging processes in large cohorts of older Black, Hispanic and White survivors that explain relationships between health determinants and quality of life (e.g., via stress signaling and downstream effects on cellular aging via inflammatory gene expression), 2) define mechanistic pathways suggested by cohort results and test the impact of interventions targeting those pathways in a preclinical model of cancer survivorship and 3) translate results to practice and policy. During my continuously NIH-funded research career, I have made transformative contributions that support my proposed research program. There are few population scientists with the unique background and proven track record to successfully conduct this in-depth research program spanning the full translational continuum from preclinical to cohort studies and practice and policy. Collaboration with scientists from outside my discipline will support my success and generate novel insights. The newly established Georgetown Lombardi Institute on Cancer and Aging that I lead and exceptional institutional commitment and infrastructure provide an exceptional environment. This Outstanding Investigator Award will provide me with the stability needed to accelerate knowledge in an understudied research area with high public health significance and clinical relevance. Identification and testing of aging mechanistically-based interventions will support efforts to tailor clinical care for the burgeoning older minority survivor population and could to transform how we approach cancer disparities in the context of aging.

到 2030 年，美国 2200 万癌症幸存者中的四分之三将是 65 岁及以上，并且老年人的数量 西班牙裔和黑人幸存者的成长速度将是白人的三倍。这些不断变化的人口统计数据是 由于缺乏指导老年幸存者（尤其是老年人）护理的证据，导致癌症护理危机 实际上缺乏数据的种族/族裔幸存者。填补这些空白需要了解 健康差异、衰老和癌症交叉点上的几种复杂的多向关系。 与年长的白人幸存者相比，年长的少数族裔幸存者一生中接触过更多的 健康的不利社会决定因素。这些暴露会加速老化过程。衰老会增加风险 通过累积的损伤和突变发展成癌症。反过来，癌症及其治疗方法也是疾病 衰老的驱动因素。这些交叉力量共同作用可能会加剧当前的种族/民族癌症 老年幸存者的健康和生活质量存在差异。杰出研究者奖的愿景 是通过提供对癌症差异的机械理解来从根本上改变我们处理癌症差异的方式 细胞衰老在健康社会决定因素与生存结果之间关系中的作用。我会 使用将多层次差异框架与肿瘤学和老年科学相结合的概念模型 使用转录组学和其他组学分析、表观遗传学、机器学习进行研究的观点， 中介模型、综合综合和群体模拟方法。我的跨学科的广泛目标 研究计划的目的是：1）发现大量老年黑人、西班牙裔和西班牙裔的细胞衰老过程。 白人幸存者解释了健康决定因素与生活质量之间的关系（例如，通过压力 通过炎症基因表达对细胞衰老的信号传导和下游影响），2）定义机制 队列结果建议的途径，并测试针对这些途径的干预措施的影响 癌症生存的临床前模型；3) 将结果转化为实践和政策。在我不断的 NIH 资助的研究生涯，我做出了变革性的贡献来支持我提出的研究 程序。很少有人口科学家拥有独特的背景和良好的成功记录 开展这项涵盖从临床前到队列的完整转化连续体的深入研究计划 研究、实践和政策。与我学科之外的科学家合作将支持我的成功 并产生新颖的见解。新成立的乔治城隆巴迪癌症与衰老研究所 领先且卓越的机构承诺和基础设施提供了卓越的环境。这 杰出研究者奖将为我提供加速知识获取所需的稳定性 具有高度公共卫生意义和临床相关性的研究领域。鉴定与测试 基于老龄化机制的干预措施将支持为新兴老年人量身定制临床护理的努力 少数民族幸存者人口，并可以改变我们在老龄化背景下处理癌症差异的方式。