As people age, they experience declining physical performance, which is associated with diminished
quality of life, augmented health care costs, and is a strong predictor of morbidity and mortality. Thus,
uncovering mechanisms that underlie age-associated mobility decline and identifying reliable biomarkers
to predict this decline is imperative for the development of interventions to maintain physical ability with
age. Mitochondria generate chemical energy to support homeostatic function of most cells in the body,
and mitochondrial dysfunction is linked to age-associated decline in physical performance. This has been
studied predominantly in skeletal muscle mitochondria since muscle function is central to physical ability.
However, it is recognized that muscle function is not the sole determinant of mobility, and that input from
other organ systems (cardiovascular and central nervous system) is also required. While age associated
mitochondrial dysfunction has been observed across all organ systems, the contribution of this systemic
bioenergetic dysfunction to age-associated mobility decline has not been assessed. The current study
brings together two PIs with expertise in mitochondrial biology who have independently optimized and
validated complementary assays (high resolution respirometery and Seahorse extracellular flux analysis)
for the measurement of systemic bioenergetic function utilizing blood cells (platelets and peripheral blood
mononuclear cells). Preliminary data using these assays show that blood cell mitochondrial function
reflects bioenergetics of solid tissues (e.g. skeletal muscle, heart, lung, brain) and correlates with multiple
measures of physical ability. However, it is unknown whether blood cell bioenergetics reflect skeletal
muscle function or are predictive of mobility decline in older adults. The Study of Muscle, Mobility and
Aging (SOMMA) is a multi-site longitudinal study of older adults (=70 years; n=875). SOMMA focuses on
the relationship between skeletal muscle mitochondria and mobility decline and will obtain skeletal
muscle biopsies to measure mitochondrial function in all participants. Physical performance measures
will at baseline and three years follow-up. The current proposal is an ancillary study that synergizes with
SOMMA to add blood cell bioenergetic measurements in all SOMMA participants at baseline as well as
at the three year follow up visit. Using these data, we will test whether blood cell bioenergetics are 1)
reflective of skeletal muscle mass and function, 2) are associated with physical performance measures
(400 m walk), and 3) are predictive of physical performance decline in older adults. Completion of this
study will elucidate systemic mitochondrial changes that are associated with age-related physical decline,
and potentially establish blood cell bioenergetics as a biomarker of systemic mitochondrial function that
can be utilized as a surrogate for muscle biopsies, and as a predictor of mobility decline in the aging
population.