Evidence for inefficient contraction and abnormal mitochondrial activity in sarcopenia using magnetic resonance spectroscopy.

BACKGROUND: Mitochondrial dysfunction has been implicated in sarcopenia. 31 P magnetic resonance spectroscopy (MRS) enables non-invasive measurement of adenosine triphosphate (ATP) synthesis rates to probe mitochondrial function. Here, we assessed muscle energetics in older sarcopenic and non-sarcopenic men and compared with muscle biopsy-derived markers of mitochondrial function. METHODS: Twenty Chinese men with sarcopenia (SARC, age = 73.1 ± 4.1 years) and 19 healthy aged and sex-matched controls (CON, age = 70.3 ± 4.2 years) underwent assessment of strength, physical performance, and magnetic resonance imaging. Concentrations of phosphocreatine (PCr), ATP and inorganic phosphate (Pi) as well as muscle pH were measured at rest and during an interleaved rest-exercise protocol to probe muscle mitochondrial function. Results were compared to biopsy-derived mitochondrial complex activity and expression to understand underlying metabolic perturbations. RESULTS: Despite matched muscle contractile power (strength/cross-sectional area), the ATP contractile cost was higher in SARC compared with CON (low-intensity exercise: 1.06 ± 0.59 vs. 0.57 ± 0.22, moderate: 0.93 ± 0.43 vs. 0.58 ± 0.68, high: 0.70 ± 0.57 vs. 0.43 ± 0.51 mmol L-1  min-1  bar-1  cm-2 , P = 0.003, <0.0001 and <0.0001, respectively). Post-exercise mitochondrial oxidative synthesis rates (a marker of mitochondrial function) tended to be longer in SARC but did not reach significance (17.3 ± 6.4 vs. 14.6 ± 6.5 mmol L-1  min-1 , P = 0.2). However, relative increases in end-exercise ADP in SARC (31.8 ± 9.9 vs. 24.0 ± 7.3 mmol L-1 , P = 0.008) may have been a compensatory mechanism. Mitochondrial complex activity was found to be associated with exercise-induced drops in PCr [citrate synthetase activity (CS), Spearman correlation rho = -0.42, P = 0.03] and end-exercise ADP (complex III, rho = -0.52, P = 0.01; CS rho = -0.45, P = 0.02; SDH rho = -0.45, P = 0.03), with CS also being strongly associated with the PCr recovery rate following low intensity exercise (rho = -0.47, P = 0.02), and the cost of contraction at high intensity (rho = -0.54, P = 0.02). Interestingly, at high intensity, the fractional contribution of oxidative phosphorylation to exercise was correlated with activity in complex II (rho = 0.5, P = 0.03), CS (rho = 0.47, P = 0.02) and SDH (rho = 0.46, P = 0.03), linking increased mitochondrial complex activity with increased ability to generate energy through oxidative pathways. CONCLUSIONS: This study used 31 P MRS to assess ATP utilization and resynthesis in sarcopenic muscle and demonstrated abnormal increases in the energy cost during exercise and perturbed mitochondrial energetics in recovery. Associations between mitochondrial complex activity and the fractional contribution to energy requirement during exercise indicate increased ability to generate energy oxidatively in those with better mitochondrial complex activity.

Is Trunk Posture in Walking a Better Marker than Gait Speed in Predicting Decline in Function and Subsequent Frailty?

BACKGROUND: Many recent guidelines and consensus on sarcopenia have incorporated gait speed and grip strength as diagnostic criteria without addressing early posture changes adopted to maintain gait speed before weakness is clinically evident. OBJECTIVES: Older adults are known to compensate well for declining physiological reserve through environmental modification and posture adaptation. This study aimed to analyze and identify significant posture adaptation in older adults that is required to maintain gait speed in the face of increasing vulnerability. This would be a useful guide for early posture correction exercise interventions to prevent further decline, in addition to traditional gait, balance, and strength training. DESIGN: A community-based cross-sectional study. SETTING AND PARTICIPANTS: The participants comprised 90 healthy community-dwelling Chinese men between the ages of 60 and 80 years and 20 Chinese adults between the ages of 21 and 50 years within the normal BMI range as a comparison group. MEASUREMENTS: All the participants underwent handgrip strength testing, 6-minute walk, timed up-and-go (TUG), and motion analysis for gait characteristics. Low function was characterized by slow walking speed (<1.0 m/s) and/or slow TUG (>10 seconds), whereas low strength was determined by hand grip dynamometer testing (<26 kg). The degree of frailty was classified using the Canadian Study for Health and Ageing Clinical Frailty Scale (CSHA-CFS) to differentiate between healthy and vulnerable older adults. RESULTS: As expected, the vulnerable older adults had lower functional performance and strength compared with the healthy older adults group. However, a significant number demonstrated posture adaptations in walking in all 3 groups, including those who maintained a good walking speed (>1.0 m/s). The extent of such adaptation was larger in the vulnerable group as compared with the healthy group. CONCLUSION: Although gait speed is a robust parameter for screening older adults for sarcopenia and frailty, our data suggest that identifying trunk posture adaptation before the onset of decline in gait speed will help in planning interventions in the at-risk community-dwelling older adults even before gait speed declines.