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. 2018 Apr;17(2):e12725.
doi: 10.1111/acel.12725. Epub 2018 Jan 21.

Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore Longitudinal Study of Aging

Marta Gonzalez-Freire  1 , Paul Scalzo  1 , Jarod D'Agostino  2 , Zenobia A Moore  1 , Alberto Diaz-Ruiz  3 , Elisa Fabbri  1 , Ariel Zane  1 , Brian Chen  1 , Kevin G Becker  4 , Elin Lehrmann  4 , Linda Zukley  2 , Chee W Chia  5 , Toshiko Tanaka  1 , Paul M Coen  6 , Michel Bernier  3 , Rafael de Cabo  3 , Luigi Ferrucci  1
Affiliations

Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore Longitudinal Study of Aging

Marta Gonzalez-Freire et al. Aging Cell. 2018 Apr.

Abstract

Mitochondrial function in human skeletal muscle declines with age. Most evidence for this decline comes from studies that assessed mitochondrial function indirectly, and the impact of such deterioration with respect to physical function has not been clearly delineated. We hypothesized that mitochondrial respiration in permeabilized human muscle fibers declines with age and correlates with phosphocreatine postexercise recovery rate (kPCr), muscle performance, and aerobic fitness. Mitochondrial respiration was assessed by high-resolution respirometry in saponin-permeabilized fibers from vastus lateralis muscle biopsies of 38 participants from the Baltimore Longitudinal Study of Aging (BLSA; 21 men, age 24-91 years) who also had available measures of peak oxygen consumption (VO2max ) from treadmill tests, gait speed in different tasks, 31 P magnetic resonance spectroscopy, isokinetic knee extension, and grip strength. Results indicated a significant reduction in mitochondrial respiration with age (p < .05) that was independent of other potential confounders. Mitochondrial respiratory capacity was also associated with VO2max , muscle strength, kPCr, and time to complete a 400-m walk (p < .05). A negative trend toward significance (p = .074) was observed between mitochondrial respiration and BMI. Finally, transcriptional profiling revealed a reduced mRNA expression of mitochondrial gene networks with aging (p < .05). Overall, our findings reinforce the notion that mitochondrial function declines with age and may contribute to age-associated loss of muscle performance and cardiorespiratory fitness.

Keywords: aging; mitochondria; muscle performance; oxidative capacity; skeletal muscle.

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Figures

Figure 1
Figure 1
Representative scatterplots showing the association of mitochondrial respiration with age. The association between oxygen consumption at 5ADP (left panel), 2 mm ADP (defined as State 3, center panel), and AUC (right panel) with age is presented after adjustment for sex and BMI. AUC, area under the curve
Figure 2
Figure 2
Association of the mitochondrial respiration derived from the different concentrations of ADP in function of age. Line graphs showing the p‐values (upper panel) and r (bottom panel) of the bivariate association between ADP concentrations and age (model not adjusted, adjusted for sex, and then adjusted for sex and BMI). 1ADP to 8ADP, ADP concentrations of 31.25 μm to 1 mm; State 3: 2 mm; State 4: malate (5 mm), glutamate (10 mm), succinate (10 mm)
Figure 3
Figure 3
Age‐associated alterations in skeletal muscle transcriptome. (a) Principal component analysis (PCA) showing a clear effect of aging in the skeletal muscle transcriptome among the different age groups. (b) Venn diagram illustrating the number of significantly up‐ (red) and down‐regulated (blue) genes observed in the indicated pairwise comparisons. (c) Venn diagram illustrating the number of significantly up (red)‐ and down‐regulated (blue) GO Terms observed in the indicated pairwise comparisons. (d) Graphical representation of a partial list of significant GO Terms shared between the MA_Y and O_Y pairwise comparisons, with the Z‐score values of O_Y depicted. MA, middle‐aged (N = 4), O, old (N = 12); Y, young (N = 3)
Figure 4
Figure 4
Hierarchical clustering correlation heatmap showing the association between all the covariates included in the analysis. Mitochondrial measurements are clustered with measurements related to oxidative capacity. Positive correlations are displayed in green and negative correlations in red color. Color intensity is proportional to the correlation coefficients
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