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

基本信息

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
项目类别：
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

项目摘要

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，2200万美国癌症幸存者中有四分之三的年龄较大，年龄较大西班牙裔和黑人幸存者的增长速度将比白人快三倍。这些不断变化的人口统计学是由于缺乏证据来指导年长的幸存者，尤其是年长的证据，驱动癌症护理危机实际上缺乏数据的种族/族裔幸存者。填补这些空白将需要了解在健康差异，衰老和癌症的交汇处，几种复杂的多向关系。与年长的白人幸存者相比，年长的种族/少数民族幸存者对不利的健康决定因素。这些暴露会加速衰老过程。衰老增加了风险通过积累的损害和突变来发展癌症。癌症及其疗法反过来是疾病衰老的驱动力。这些相交的力量在一起可能加剧当前的种族/种族癌症年长幸存者的健康和生活质量的差异。这个杰出调查员奖的愿景是从根本上转移我们如何通过提供对癌症差异的方式细胞衰老在健康决定因素与生存结果之间的关系中的作用。我会使用将多层差异框架与肿瘤学和Geroscience集成的概念模型使用转录组和其他组合分析，表观遗传学，机器学习，进行研究的观点调解模型，元合成和种群模拟方法。我跨学科的广泛目标研究计划是：1）在大量较老的黑人，西班牙裔和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）定义机械队列结果提出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和3）将结果转化为实践和政策。在我不断的过程中 NIH资助的研究生涯，我做出了转型贡献，以支持我的拟议研究程序。人口科学家很少有独特的背景和可靠的记录来成功进行这个深入的研究计划，跨越了从临床前的完整转化连续性研究，实践和政策。与我学科外部科学家的合作将支持我的成功并产生新颖的见解。新成立的乔治敦伦巴第癌和衰老研究所领导和非凡的机构承诺和基础设施提供了一个特殊的环境。这杰出的调查员奖将为我提供加速知识所需的稳定性研究领域的研究领域具有很高的公共健康意义和临床相关性。识别和测试基于机械的老化的干预措施将支持为临时较老的临床护理量身定制临床护理的努力少数族裔幸存者人口，可以改变我们在衰老的情况下如何应对癌症差异。