Coen, P. M. | bioRxiv Science

bioRxiv2017

Metabolite profile and mitochondrial energetics characterize poor early recovery of muscle mass following hind limb unloading in old mice

The progression of age-related sarcopenia can be accelerated by impaired recovery of muscle mass following periods of disuse due to illness or immobilization. The molecular underpinnings of poor recovery of aging muscle following disuse remain largely unknown. However, recent evidence suggests that mitochondrial energetics may play an important role. Here, we report that 22-24 month old mice with low muscle mass and insulin resistance display poor early recovery of muscle mass following 10 days of hind limb unloading. We took an unbiased approach to identify changes in energy metabolism gene expression and metabolite pools and show for the first time that persistent mitochondrial dysfunction, dysregulated fatty acid {beta}-oxidation and elevated H2O2 emission underlie poor early recovery of muscle mass following a period of disuse in old mice. Importantly, this is linked to more severe whole-body insulin resistance. The findings suggest that muscle fuel metabolism and mitochondrial energetics should be a focus for mining therapeutic targets to improve recovery of muscle mass following periods of disuse in older animals.

physiology↗

bioRxiv2017

Physical activity unveils the relationship between mitochondrial energetics, muscle quality and physical function in older adults

BackgroundThe concept of mitochondrial dysfunction in aging muscle is highly controversial. In addition, emerging evidence suggests that reduced muscle oxidative capacity and efficiency underlie the etiology of mobility loss in older adults. Here, we hypothesized that studying well phenotyped older cohorts across a wide range of physical activity would unveil a range of mitochondrial function in skeletal muscle and in turn allow us to more clearly examine the impact of age per se on mitochondrial energetics. This also enabled us to more clearly define the relationships between mitochondrial energetics and muscle lipid content with clinically relevant assessments of muscle and physical function.\n\nMethodsThirty-nine volunteers were recruited to the following study groups; Young Active (YA, n=2F/8M, age=31.2{+/-}5.4 yrs.). Older Active (OA, n=2F/8M, age=67.5{+/-}2.7 yrs.) and Older Sedentary (OS, n=8F/11M, age=70.7{+/-}4.7 yrs.). Participants completed a graded exercise test to determine fitness (VO2peak), a submaximal exercise test to determine exercise efficiency, and daily physical activity (PA) was recorded using a tri-axial armband accelerometer. Mitochondrial energetics were determined by 1) 31P magnetic resonance spectroscopy and 2) respirometry of fiber bundles from vastus lateralis biopsies. Quadriceps function was assessed by isokinetic dynamometry and physical function by the short physical performance battery (SPPB) and stair climb test.\n\nResultsDaily PA energy expenditure was significantly lower in OS, compared to YA and OA groups. Despite fitness being higher in YA compared to OA and OS, mitochondrial respiration, ATPMax, P/O ratio and exercise efficiency were similar in YA and OA groups and were significantly lower in OS. P/O ratio was correlated with exercise efficiency. Time to complete the stair climb and repeated chair stand tests was significantly greater for OS. Interestingly, ATPMax was related to muscle contractile performance and physical function.\n\nConclusionsOlder adults who maintain a high amount of physical activity have better mitochondrial capacity, similar to highly active younger adults, and this is related to their better muscle quality, exercise efficiency and physical performance. This suggests that mitochondria could be an important therapeutic target for sedentary aging associated conditions including sarcopenia, dynapenia and loss of physical function.

physiology↗