Although it is well understood that physical performance in older age is among the best predictors of independence and disability, and that social determinants play a critical role in shaping physical function, the biologic mechanisms underlying these relationships are poorly understood. The study of mitochondria function offers a promising cellular mechanism by which social experiences become biologically embedded. Mitochondrial dysfunction, recently identified as a “hallmark of aging”, also underlies age-related pathologies in multiple systems, including cardiovascular, neuronal, and musculoskeletal. More specifically, mitochondrial function is highly associated with worsening physical performance among adults. However, to date, there are no field studies exploring whether mitochondrial function are related to both gold-standard measures of physical performance and social determinants of health in population health studies. Recent understanding of the contribution of mitochondrial function as a biologic mechanism to aging has been hampered by two major methodological challenges: First, the assessment of mitochondrial function has been traditionally limited to tissue-specific measures of mitochondrial bioenergetics. Second, blood-based measurements of mitochondrial bioenergetics have been recently developed on fresh whole blood, a limitation which precludes the ability to harness existing longitudinal data from frozen samples stored in biorepositories from aging population studies. This proposal will overcome these obstacles by leveraging blood-based markers of mitochondrial bioenergetics via the respirometry in frozen samples (RIFS) method while linking these novel measures to upstream, multidimensional aspects of socioeconomic position and gold-standard measures of physical functioning and performance. Our approach offers a unique opportunity to harness cost-effective, minimally invasive techniques from frozen blood, laying the groundwork for larger-scale population health studies. We leverage data the Health and Retirement Study (HRS) which contains gold-standard measures of physical functioning and performance, life course socioeconomic measures, and the potential to analyze frozen PBMC samples to obtain measures of systemic mitochondrial bioenergetic capacity. The specific aims are to (1) Examine the association between the socioeconomic position and systemic markers of mitochondrial bioenergetic capacity; (2) Examine the association between mitochondrial bioenergetic capacity and multiple measures of physical performance and function, (3) Preliminarily test whether systemic markers of mitochondrial bioenergetic capacity mediate the link between the socioeconomic position and physical performance and function. This proposal utilizes highly innovative technology to provide evidence that mitochondrial bioenergetic capacity may serve as a biologic mechanism linking socioeconomic position to downstream physical functioning and performance. The RIFS method has unlimited potential to open access to large-scale population-based aging studies with existing biorepositories that have been collecting social data and banking frozen blood samples.
Funding:
Health and Human Services, Department of-National Institutes of Health
Funding Period:
08/01/2024 to 07/31/2026