Examining the relationship between blood-based mitochondrial bioenergetic capacity in frozen samples, socioeconomic position, and physical functioning

Physical function in older age is among the best predictors of independence and disability. Social determinants of health (SDOH) play a critical role in shaping physical function. Yet, the biologic mechanisms linking SDOH to physical performance are poorly understood. Mitochondrial function (“bioenergetics”), defined by changes in

the capacity to generate cellular energy in the form of adenosine triphosphate (ATP), becomes impaired with advancing age. Mitochondrial bioenergetic decline represents a novel cellular mechanism by which social experiences can become biologically embedded. Previous studies examining the biologic underpinnings of

how SDOH determinants influence physical functioning have focused on non-specific, global biologic processes (i.e., allostatic load, whole-body inflammation). In contrast, blood-based measures of mitochondrial bioenergetic capacity are easier to obtain and biologically specific. To date, there are no population-based

studies exploring whether mitochondrial function is related to measures of both physical function and SDOH, specifically the role of socioeconomic position, in population health studies. Our understanding of the contributions of mitochondrial bioenergetics to population health has been hampered by two major

methodological challenges. First, mitochondrial function is traditionally measured using invasive, labor intensive, tissue-specific measures (i.e., skeletal muscle), thereby limiting its use in population-based studies. Second, blood-based bioenergetic profiling requires the analysis of live samples, a limitation which precludes

harnessing longitudinal data from existing biorepositories from aging population studies. This proposal overcomes these obstacles by leveraging blood-based markers of mitochondrial bioenergetics via the innovative respirometry in frozen samples (RIFS) method, an emerging methodology that reconstitutes

maximal mitochondrial respiration in previously frozen samples, even those that have undergone multiple freeze-thaw cycles. This approach is cost-effective and uses minimally invasive techniques from frozen blood, laying the groundwork for larger-scale population health studies. We leverage data and stored samples from

the nationally representative Health and Retirement Study (HRS), a large, population-based study of adults over age 50. The specific aims of this proposal are to: (1) Test the reliability and validity of systemic markers of mitochondrial bioenergetic capacity using the RIFS method in a field-collected, population health study; (2)

Examine the association between markers of mitochondrial systemic bioenergetic capacity and multiple measures of physical performance and function, and; (3) Examine the association between socioeconomic position and systemic markers of mitochondrial bioenergetic capacity. The results of this study will provide

important evidence that measures of mitochondrial function, obtained via the RIFS method, can be related to social factors and other important aging-related outcomes and has broad potential to, for the first time, open access to large-scale population-based aging studies with existing biorepositories.