Striatal Dopamine and Skeletal Muscle Energy Metabolism in Older Adults

Abstract

Dopamine (DA) in the central nervous system is considered a master regulator of mobility performance and vigor, but its mechanistic relationship with skeletal muscle energetics is unclear. We tested the cross-sectional association of striatal DA and skeletal muscle mitochondrial function in 146 older adults participating in the Study of Muscle, Mobility and Aging (75.4 years old, 54% women). Striatal DA was measured using (+)-a-[¹¹C] dihydrotetrabenazine (DTBZ) PET imaging for the limbic, sensorimotor, and executive control subregions. Mitochondrial capacity to produce ATP (ATP_max, mM ATP/s) was measured in vivo using ³¹P magnetic resonance spectroscopy after repeated voluntary muscle contractions. Ex-vivo respirometry assays from biopsies of resting muscle captured complementary aspects of mitochondrial function under optimal conditions. In multivariable linear regression models, [¹¹C]DTBZ in the limbic striatum, but not other subregions, was positively associated with greater ATPmax in vivo, independent of demographics, muscle volume, leg power, white matter hyperintensities, gray matter atrophy, moderate-to-vigorous physical activity and diabetes (β = 0.275, standard error 0.108, p=0.019). [¹¹C]DTBZ was not associated with the ex-vivo mitochondrial respiration markers (p>0.2). The role of striatal limbic DA and the energetic capacity of skeletal muscles should be further investigated in older adults.