Striatal dopamine in the limbic subregion, but not other subregions, was positively associated with greater skeletal muscle mitochondrial ATP production capacity in vivo in older adults, independent of multiple confounders.
Key Findings
Results
Limbic striatal dopamine was positively associated with in vivo skeletal muscle mitochondrial ATP production capacity in older adults.
Association found in multivariable linear regression models with β = 0.275, standard error 0.108, p = .019
The association was independent of demographics, muscle volume, leg power, white matter hyperintensities, gray matter atrophy, moderate-to-vigorous physical activity, and diabetes
Striatal DA was measured using (+)-a-[11C] dihydrotetrabenazine (DTBZ) PET imaging
Mitochondrial capacity to produce ATP (ATPmax, mM ATP/s) was measured in vivo using 31P magnetic resonance spectroscopy after repeated voluntary muscle contractions
Sample consisted of 146 older adults with mean age 75.4 years, 54% women, from the Study of Muscle, Mobility and Aging (SOMMA)
Results
The positive association between striatal dopamine and skeletal muscle energetics was specific to the limbic striatal subregion and not observed in sensorimotor or executive control subregions.
[11C]DTBZ in the sensorimotor and executive control striatal subregions was not significantly associated with ATPmax
Three striatal subregions were examined: limbic, sensorimotor, and executive control
Only the limbic striatum showed a statistically significant association (p = .019)
Results
Striatal dopamine was not associated with ex vivo mitochondrial respiration markers measured from muscle biopsies.
p > .2 for all ex-vivo mitochondrial respiration markers
Ex-vivo respirometry assays were performed from biopsies of resting muscle
Ex-vivo assays were described as capturing 'complementary aspects of mitochondrial function under optimal conditions'
The null finding for ex-vivo measures contrasts with the significant positive finding for in vivo ATPmax
Methods
The study used a cross-sectional design in older adults participating in the Study of Muscle, Mobility and Aging (SOMMA).
146 older adults were included in the analysis
Mean age was 75.4 years and 54% were women
Both PET neuroimaging and skeletal muscle functional assessments (in vivo 31P MRS and ex vivo respirometry) were obtained from the same participants
Covariates included demographics, muscle volume, leg power, white matter hyperintensities, gray matter atrophy, moderate-to-vigorous physical activity, and diabetes
Background
Dopamine in the central nervous system is considered a master regulator of mobility performance and vigor, but its mechanistic relationship with skeletal muscle energetics was previously unclear.
The study was motivated by an unclear mechanistic relationship between striatal DA and skeletal muscle energetics
Both striatal dopamine and skeletal muscle mitochondrial function are relevant to mobility in older adults
The authors conclude that 'the role of striatal limbic DA and the energetic capacity of skeletal muscles should be further investigated in older adults'
Rosano C, Bohnen N, Lopresti B, Chahine L, Barnes H, Studenski S, et al.. (2026). Striatal dopamine and skeletal muscle energy metabolism in older adults.. The journals of gerontology. Series A, Biological sciences and medical sciences. https://doi.org/10.1093/gerona/glag039