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

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.