Mitochondrial respiratory chain function and content are preserved in the skeletal muscle of active very old men and women

Abstract

Introduction: The loss of mitochondrial function and content have been implicated in sarcopenia although they have been little studied in the very old, the group in which sarcopenia is most common. In this pilot study, our aim was to determine if mitochondrial respiratory chain function and content are preserved among healthy 85-year-olds.

Methods: We recruited 19 participants (11 female) through their general practitioner and assessed their medical history, functional status and self-reported physical activity. We identified sarcopenia using grip strength, Timed Up-and-Go and bioimpedance analysis. We assessed mitochondrial respiratory chain function using phosphorous magnetic resonance spectroscopy, estimating τ_1/2 PCr, the recovery half-time of phosphocreatine in the calf muscles following a bout of aerobic exercise. We performed a biopsy of the vastus lateralis muscle and assessed mitochondrial respiratory chain content by measuring levels of subunits of complex I and IV of the respiratory chain, expressed as Z-scores relative to that in young controls.

Results: Participants had a median (IQR) of 2 (1,3) long-term conditions, reported regular aerobic physical activity, and one participant (5.3%) had sarcopenia. Sixteen participants completed the magnetic resonance protocol and the mean (SD) τ_1/2 PCr of 35.6 (11.3) seconds was in keeping with preserved mitochondrial function. Seven participants underwent muscle biopsy and the mean fibre Z-scores were -0.7 (0.7) and -0.2 (0.4) for complexes I and IV, respectively, suggesting preserved content of mitochondrial respiratory chain enzymes.

Conclusion: Muscle mitochondrial respiratory chain function and content are preserved in a sample of active, well-functioning 85-year-olds, among whom sarcopenia was uncommon. The results from this study will help inform future work examining the association between muscle mitochondrial deficiency and sarcopenia.

Keywords: Ageing; Mitochondrial function; Muscle mass; Physical performance; Sarcopenia.

Fig. 1

Assessment of mitochondrial function and content. Sample results for mitochondrial function and content (NB two different participants are shown). A. Exponential recovery curve for phosphocreatine following exercise. τ_1/2 PCr for participant shown is 36.6 s. B. Quadruple immunofluorescence. Mean Z-scores from participant shown of 0.6 for complex IV (MTCOI) and 0.1 for complex I (NDUFB8).