scholarly journals A Plasma Proteomic Signature of Skeletal Muscle Mitochondrial Function

2020 ◽  
Vol 21 (24) ◽  
pp. 9540
Author(s):  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Ceereena Ubaida-Mohien ◽  
Giovanna Fantoni ◽  
Julián Candia ◽  
...  

Although mitochondrial dysfunction has been implicated in aging, physical function decline, and several age-related diseases, an accessible and affordable measure of mitochondrial health is still lacking. In this study we identified the proteomic signature of muscular mitochondrial oxidative capacity in plasma. In 165 adults, we analyzed the association between concentrations of plasma proteins, measured using the SOMAscan assay, and skeletal muscle maximal oxidative phosphorylation capacity assessed as post-exercise phosphocreatine recovery time constant (τPCr) by phosphorous magnetic resonance spectroscopy. Out of 1301 proteins analyzed, we identified 87 proteins significantly associated with τPCr, adjusting for age, sex, and phosphocreatine depletion. Sixty proteins were positively correlated with better oxidative capacity, while 27 proteins were correlated with poorer capacity. Specific clusters of plasma proteins were enriched in the following pathways: homeostasis of energy metabolism, proteostasis, response to oxidative stress, and inflammation. The generalizability of these findings would benefit from replication in an independent cohort and in longitudinal analyses.

2000 ◽  
Vol 89 (3) ◽  
pp. 1072-1078 ◽  
Author(s):  
Jane A. Kent-Braun ◽  
Alexander V. Ng

It has been suggested that a decline in skeletal muscle oxidative capacity is a general consequence of aging in humans. However, previous studies have not always controlled for the effects of varying levels of physical activity on muscle oxidative capacity. To test the hypothesis that, when matched for comparable habitual physical activity levels, there would be no age-related decline in the oxidative capacity of a locomotor muscle, the postexercise recovery time of phosphocreatine was compared in the tibialis anterior muscle of young [ n = 19; 33.8 ± 4.8 (SD) yr] and older [ n = 18; 75.5 ± 4.5 yr] healthy women and men of similar, relatively low, activity levels. The intramuscular metabolic measurements were accomplished by using phosphorus magnetic resonance spectroscopy. The results indicate that there was no age effect on the postexercise recovery time of phosphocreatine recovery, thus supporting the stated hypothesis. These data suggest that there is no requisite decline in skeletal muscle oxidative capacity with aging in humans, at least through the seventh decade.


2020 ◽  
Vol 75 (12) ◽  
pp. 2262-2268 ◽  
Author(s):  
Marta Zampino ◽  
Richard D Semba ◽  
Fatemeh Adelnia ◽  
Richard G Spencer ◽  
Kenneth W Fishbein ◽  
...  

Abstract Resting metabolic rate (RMR) tends to decline with aging. The age-trajectory of decline in RMR is similar to changes that occur in muscle mass, muscle strength, and fitness, but while the decline in these phenotypes has been related to changes of mitochondrial function and oxidative capacity, whether lower RMR is associated with poorer mitochondrial oxidative capacity is unknown. In 619 participants of the Baltimore Longitudinal Study of Aging, we analyzed the cross-sectional association between RMR (kcal/day), assessed by indirect calorimetry, and skeletal muscle maximal oxidative phosphorylation capacity, assessed as postexercise phosphocreatine recovery time constant (τ PCr), by phosphorous magnetic resonance spectroscopy. Linear regression models were used to evaluate the relationship between τ PCr and RMR, adjusting for potential confounders. Independent of age, sex, lean body mass, muscle density, and fat mass, higher RMR was significantly associated with shorter τ PCr, indicating greater mitochondrial oxidative capacity. Higher RMR is associated with a higher mitochondrial oxidative capacity in skeletal muscle. This association may reflect a relationship between better muscle quality and greater mitochondrial health.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 124-124
Author(s):  
Marta Zampino ◽  
Richard Semba ◽  
Fatemeh Adelnia ◽  
Jennifer Schrack ◽  
Richard Spencer ◽  
...  

Abstract Resting metabolic rate (RMR) tends to decline with aging. The age-trajectory of decline in RMR is similar to changes that occur in muscle mass, muscle strength and fitness. However, while the decline in these phenotypes have been related to changes of mitochondrial function and oxidative capacity, whether lower RMR is associated with poorer mitochondrial oxidative capacity is unknown. In 619 participants of the Baltimore Longitudinal Study of Aging, we analyzed the cross-sectional association between RMR (kcal/day), assessed by indirect calorimetry, and skeletal muscle maximal oxidative phosphorylation capacity, assessed as post-exercise phosphocreatine recovery time constant (tau-PCr), by phosphorous magnetic resonance spectroscopy. Linear regression models were used to evaluate the relationship between tau-PCr and RMR, adjusting for potential confounders. We found that independent of age, sex, lean body mass, muscle density and fat mass, higher RMR was significantly associated with shorter tau-PCr, indicating greater mitochondrial oxidative capacity. In conclusion, higher RMR appears to be associated with a higher mitochondrial oxidative capacity in skeletal muscle. This association may reflect a relationship between better muscle quality and greater mitochondrial health.


Author(s):  
Daniele A. Cardinale ◽  
Kasper D. Gejl ◽  
Kristine Grøsfjeld Petersen ◽  
Joachim Nielsen ◽  
Niels Ørtenblad ◽  
...  

Aim: The maintenance of healthy and functional mitochondria is the result of a complex mitochondrial turnover and herein quality-control program which includes both mitochondrial biogenesis and autophagy of mitochondria. The aim of this study was to examine the effect of an intensified training load on skeletal muscle mitochondrial quality control in relation to changes in mitochondrial oxidative capacity, maximal oxygen consumption and performance in highly trained endurance athletes. Methods: 27 elite endurance athletes performed high intensity interval exercise followed by moderate intensity continuous exercise 3 days per week for 4 weeks in addition to their usual volume of training. Mitochondrial oxidative capacity, abundance of mitochondrial proteins, markers of autophagy and antioxidant capacity of skeletal muscle were assessed in skeletal muscle biopsies before and after the intensified training period. Results: The intensified training period increased several autophagy markers suggesting an increased turnover of mitochondrial and cytosolic proteins. In permeabilized muscle fibers, mitochondrial respiration was ~20 % lower after training although some markers of mitochondrial density increased by 5-50%, indicative of a reduced mitochondrial quality by the intensified training intervention. The antioxidative proteins UCP3, ANT1, and SOD2 were increased after training, whereas we found an inactivation of aconitase. In agreement with the lower aconitase activity, the amount of mitochondrial LON protease that selectively degrades oxidized aconitase, was doubled. Conclusion: Together, this suggests that mitochondrial respiratory function is impaired during the initial recovery from a period of intensified endurance training while mitochondrial quality control is slightly activated in highly trained skeletal muscle.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S84-S85
Author(s):  
Fatemeh Adelnia ◽  
Jacek Urbanek ◽  
Yusuke Osawa ◽  
Michelle Shardell ◽  
Eleanor M Simonsick ◽  
...  

Abstract Age-related decline in muscle oxidative capacity negatively affects muscle function and mobility, which may lead to disability and frailty. Whether exercise and other life-style practices reduce age-related decline in muscle oxidative capacity is unclear. We assessed whether, after accounting for age, higher daily physical activity levels are associated with greater muscle oxidative capacity. Participants included 384 adults (54.7% women) aged 22 to 92 years from the Baltimore Longitudinal Study of Aging. Muscle oxidative capacity was measured in vivo using phosphorous magnetic resonance spectroscopy. We determined the time constant for phosphocreatine recovery (τPCr, in seconds) after exercise, with lower values of τPCr reflecting greater oxidative capacity. Time spent in moderate-to-vigorous physical activity (MVPA) was assessed using accelerometers that participants wore for 5.9 ± 0.9 consecutive days in the free-living environment. In linear regression models, older age was associated with higher τPCr (β = 0.39, p-value <.001) after adjusting for sex, race, height and weight. After including MVPA as an independent variable, the standardized regression coefficient for age was attenuated by 40% to 0.22. p-value <.001). MVPA was strongly associated with lower τPCr (β = -0.33, p-value <.001) after adjusting for health status, education and smoking history and was only attenuated by 3% after additional adjustment for age. These results suggest that MVPA is strongly associated with muscle oxidative capacity independent of age, providing mechanistic insights into the health benefits of daily physical activity in older persons.


2014 ◽  
Vol 28 (7) ◽  
pp. 3211-3224 ◽  
Author(s):  
Louise Lantier ◽  
Joachim Fentz ◽  
Rémi Mounier ◽  
Jocelyne Leclerc ◽  
Jonas T. Treebak ◽  
...  

Aging Cell ◽  
2015 ◽  
Vol 14 (5) ◽  
pp. 734-743 ◽  
Author(s):  
Matthew L. Johnson ◽  
Antigoni Z. Lalia ◽  
Surendra Dasari ◽  
Maximilian Pallauf ◽  
Mark Fitch ◽  
...  

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