Striatal Dopamine and Skeletal Muscle Energy Metabolism in Older Adults

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-[ ¹¹ C] 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 ³¹ P 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, [ ¹¹ C]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). [ ¹¹ C]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.