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Perturbed muscle mitochondrial function in Sarcopenia1A*STAR-NUS Clinical Imaging Research Centre, Singapore, Singapore, 2Division of Paediatric Genetics and Metabolism, National University Hospital, 3National University of Singapore, 4A*STAR-NUS Clinical Imaging Research Centre
Synopsis
In this study we use 31P MRS in combination with Near Infra-red Spectroscopy to assess muscle mitochondrial function and changes in oxygenation in patients with Sarcopenia as to date, the etiology and molecular mechanisms of sarcopenia remain poorly understood. 10 males diagnosed with sarcopenia and 10 healthy controls were scanned where 31P MRS: A fully relaxed 31P MR spectrum data and exercise paradigm were acquired. MVC were significantly different between the sarcopenic and healthy groups (p=0.0044). Despite this, there was a tendency for increased ATP turnover in patients compared with healthy controls (44% and 66% MVC (ATP turnover p= 0.5642 44%MVC, p= 0.6128 66%MVC). Patients with sarcopenia showed significantly higher oxidative ATP synthesis ATP at 66%MVC where p= 0.0477. These results indicate that at least some of this increased requirement can be met oxidatively, with no contribution from breakdown of PCr at the end of exercise.
Introduction:
Sarcopenia, a condition causing age-related, involuntary loss of skeletal muscle and strength which can lead to functional decline and loss of independence in older adults.1 To date, the etiology and molecular mechanisms of sarcopenia remain poorly understood. In this study we use 31P MRS in combination with Near Infra-red Spectroscopy to assess muscle mitochondrial function and changes in oxygenation in patients with sarcopenia.Methods
10 males diagnosed with sarcopenia ( mean age= 74.2 ; HbA1c= 6.12; BMI = 21.52) based on AWGSOP criteria and 10 healthy age matched controls (mean age= 70.6 ; HbA1c= 5.68; BMI =23.03 ) were scanned using a Siemens 3T Trio system, using a double tuned 31P-1H coil for 31P MRS and a 16ch body coil for MRI.
MRI measurements:
31P MRS: A fully relaxed 31P MR spectrum data was acquired with the following parameters: FID sequence, TR=12000ms, BW= 3000Hz; 2048 points, 16 averages, 90* flip and for reduced coil sensitivity, a padding was placed between the coil and the calf to collect signals mainly from gastrocnemius muscle. 31P data was then acquired during the exercise paradigm using the same parameters as the fully relaxed sequence but TR=2000ms, and 840 independent acquisitions.
31P MRS data were truncated to 1024 points, zerofilled back to 2048 and 12Hz Lorentzian line broadening was added before phase correction. Fully relaxed data were then frequency corrected and averaged. Peak fitting was carried out using the AMARES algorithm in jMRUI. Adenosine triphosphate (ATP) turnover rate, oxidative ATP synthesis, fractional oxidation rate, maximum pH change during exercise and the resting state of PCr/ATP and Pi/ATP measurements were done.
Exercise:
Exercise was carried out via 0.5Hz repeated plantar flexion on a pedal ergometer system. Individual maximum voluntary contraction (MVC) was identified prior to the commencement of the scan by decreasing the pressure of the ergometer’s pedal till full compression was achieved. The paradigm made up of 1 minute rest, 3 minutes of exercise at 44% MVC, 6 minutes rest, 3 minutes of exercise at 66% MVC, 6 minutes rest, 3 minutes of exercise at 88% MVC and lastly 6 minutes rest.
NIRS measurements:
A near infra-red spectroscopy probe (OxiplexTS) was positioned on the muscle to allow measurement of muscle oxy-haemoglobin concentration [HbO2], deoxy-haemoglobin concentration [Hb] and oxygen saturation [OS]. Mean change in baseline and exercise oxidation were measured.
Results
MVC were significantly different between the sarcopenic and healthy groups (p=0.0044). Despite this, there was a tendency for increased ATP turnover in patients compared with healthy controls (44% and 66% MVC (ATP turnover p= 0.5642 44%MVC, p= 0.6128 66%MVC). Patients with sarcopenia showed significantly higher oxidative ATP synthesis ATP at 66%MVC where p= 0.0477 (figure 1). No significant difference in resting PCr/ATP, Pi/ATP, maximum PH changes and all the 3 sets of exercise oxidation between the groups. However, an increase of the baseline oxidation from the resting state to the baseline oxidation after 88% MVC was observed for both sarcopenia (p= 0.0032) and healthy groups (p= 0.0016).Conclusion
Despite lower exercise intensities, patients with sarcopenia showed increased ATP turnover during exercise. These results indicate that at least some of this increased requirement can be met oxidatively, with no contribution from breakdown of PCr at the end of exercise.Acknowledgements
No acknowledgement found.References
No reference found.Figures
