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

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $445,144

## Abstract

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 a...

## Key facts

- **NIH application ID:** 10986179
- **Project number:** 1R21AG084764-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Catherine Duchowny
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $445,144
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10986179

## Citation

> US National Institutes of Health, RePORTER application 10986179, Examining the relationship between blood-based mitochondrial bioenergetic capacity in frozen samples, socioeconomic position, and physical functioning (1R21AG084764-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10986179. Licensed CC0.

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