Chronological Age Does not Influence<i>Ex-vivo</i>Mitochondrial Respiration and Quality Control in Skeletal Muscle

Distéfano, Giovanna; Standley, Robert A.; Dubé, John J.; Carnero, Elvis Á.; Ritov, Vladimir B.; Stefanović-Račić, Maja; Toledo, Frederico G.S.; Piva, Sara R.; Goodpaster, Bret H.; Coen, Paul M.

doi:10.1093/gerona/glw102

Cited by 56 publications

(106 citation statements)

References 38 publications

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“…; Distefano et al . ). In two cases the entire mitochondrial pools were not analysed (Konopka et al .…”

Section: Discussionmentioning

confidence: 97%

“…; Distefano et al . ). Those studies also looked at fission proteins, Fis1 and/or dynamin related protein 1 (Drp1 or Dnm1L), and found these to be unchanged in muscle from young and older adults (Joseph et al .…”

Section: Discussionmentioning

confidence: 97%

“…; Distefano et al . ) and it is possible that a difference in yield of Mfn2 between the muscles being compared confounded those findings. Some general problems of fractionation are discussed in detail elsewhere (Murphy & Lamb, ).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to rodents, in humans the abundance of Mfn2 has been correlated to aerobic fitness and body composition (Distefano et al . ). Indeed, muscle Mfn2 content in humans does not seem to be affected by age (Joseph et al .…”

Section: Introductionmentioning

confidence: 97%

“…; Distefano et al . ) while Mfn2 is upregulated by 36% with continuous aerobic training in older adults aged 74 ± 3 years (Konopka et al . ).…”

Section: Introductionmentioning

confidence: 99%

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Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high‐intensity exercise training

Wyckelsma

Levinger

McKenna

et al. 2017

The Journal of Physiology

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Mitochondrial dynamics proteins are critical for mitochondrial turnover and maintenance of mitochondrial health. High-intensity interval training (HIT) is a potent training modality shown to upregulate mitochondrial content in young adults but little is known about the effects of HIT on mitochondrial dynamics proteins in older adults. This study investigated the abundance of protein markers for mitochondrial dynamics and mitochondrial content in older adults compared to young adults. It also investigated the adaptability of mitochondria to 12 weeks of HIT in older adults. Both older and younger adults showed a higher abundance of mitochondrial respiratory chain subunits COXIV and NDUFA9 in type I compared with type II fibres, with no difference between the older adults and young groups. In whole muscle homogenates, older adults had higher mitofusin-2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) contents compared to the young group. Also, older adults had higher levels of Mfn2 in type II fibres compared with young adults. Following HIT in older adults, MiD49 and Mfn2 levels were not different in whole muscle and Mfn2 content decreased in type II fibres. Increases in citrate synthase activity (55%) and mitochondrial respiratory chain subunits COXIV (37%) and NDUFA9 (48%) and mitochondrial respiratory chain complexes (∼70-100%) were observed in homogenates and/or single fibres. These findings reveal (i) a similar amount of mitochondria in muscle from young and healthy older adults and (ii) a robust increase of mitochondrial content following 12 weeks of HIT exercise in older adults.

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“…; Distefano et al . ). In two cases the entire mitochondrial pools were not analysed (Konopka et al .…”

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

“…; Distefano et al . ) while Mfn2 is upregulated by 36% with continuous aerobic training in older adults aged 74 ± 3 years (Konopka et al . ).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high‐intensity exercise training

Wyckelsma

Levinger

McKenna

et al. 2017

The Journal of Physiology

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

Distéfano

Standley

Zhang

et al. 2018

J cachexia sarcopenia muscle

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127

104

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BackgroundThe concept of mitochondrial dysfunction in ageing muscle is highly controversial. In addition, emerging evidence suggests that reduced muscle oxidative capacity and efficiency underlie the aetiology 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.MethodsThirty‐nine volunteers were recruited to the following study groups: young active (YA, n = 2 women/8 men, age = 31.2 ± 5.4 years), older active (OA, n = 2 women/8 men, age = 67.5 ± 2.7 years), and older sedentary (OS, n = 8 women/11 men, age = 70.7 ± 4.7 years). Participants completed a graded exercise test to determine fitness (VO2peak), a submaximal exercise test to determine exercise efficiency, and daily physical activity was recorded using a tri‐axial armband accelerometer. Mitochondrial energetics were determined by (i) 31P magnetic resonance spectroscopy and (ii) respirometry of fibre bundles from vastus lateralis biopsies. Quadriceps function was assessed by isokinetic dynamometry and physical function by the short physical performance battery and stair climb test.ResultsDaily physical activity energy expenditure was significantly lower in OS, compared with YA and OA groups. Despite fitness being higher in YA compared with OA and OS, mitochondrial respiration, maximum mitochondrial capacity, Maximal ATP production/Oxygen consumption (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 were significantly greater for OS. Interestingly, maximum mitochondrial capacity was related to muscle contractile performance and physical function.ConclusionsOlder 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 ageing associated conditions including sarcopenia, dynapenia, and loss of physical function.

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Mitochondrial bioenergetics are not associated with myofibrillar protein synthesis rates

Holwerda,

Dirks,

Barbeau

et al. 2024

J cachexia sarcopenia muscle

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BackgroundMitochondria represent key organelles influencing cellular homeostasis and have been implicated in the signalling events regulating protein synthesis.MethodsWe examined whether mitochondrial bioenergetics (oxidative phosphorylation and reactive oxygen species (H2O2) emission, ROS) measured in vitro in permeabilized muscle fibres represent regulatory factors for integrated daily muscle protein synthesis rates and skeletal muscle mass changes across the spectrum of physical activity, including free‐living and bed‐rest conditions: n = 19 healthy, young men (26 ± 4 years, 23.4 ± 3.3 kg/m2) and following 12 weeks of resistance‐type exercise training: n = 10 healthy older men (70 ± 3 years, 25.2 ± 2.1 kg/m2). Additionally, we evaluated the direct relationship between attenuated mitochondrial ROS emission and integrated daily myofibrillar and sarcoplasmic protein synthesis rates in genetically modified mice (mitochondrial‐targeted catalase, MCAT).ResultsNeither oxidative phosphorylation nor H2O2 emission were associated with muscle protein synthesis rates in healthy young men under free‐living conditions or following 1 week of bed rest (both P > 0.05). Greater increases in GSSG concentration were associated with greater skeletal muscle mass loss following bed rest (r = −0.49, P < 0.05). In older men, only submaximal mitochondrial oxidative phosphorylation (corrected for mitochondrial content) was positively associated with myofibrillar protein synthesis rates during exercise training (r = 0.72, P < 0.05). However, changes in oxidative phosphorylation and H2O2 emission were not associated with changes in skeletal muscle mass following training (both P > 0.05). Additionally, MCAT mice displayed no differences in myofibrillar (2.62 ± 0.22 vs. 2.75 ± 0.15%/day) and sarcoplasmic (3.68 ± 0.35 vs. 3.54 ± 0.35%/day) protein synthesis rates when compared with wild‐type mice (both P > 0.05).ConclusionsMitochondrial oxidative phosphorylation and reactive oxygen emission do not seem to represent key factors regulating muscle protein synthesis or muscle mass regulation across the spectrum of physical activity.

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Chronological Age Does not InfluenceEx-vivoMitochondrial Respiration and Quality Control in Skeletal Muscle

Abstract: Mitochondrial respiration and markers of mitochondrial dynamics (fusion and fission) are not associated with chronological age per se, but rather are more strongly associated with body mass index and cardiorespiratory fitness.

Cited by 56 publications

References 38 publications

Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high‐intensity exercise training

Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high‐intensity exercise training

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

Mitochondrial bioenergetics are not associated with myofibrillar protein synthesis rates

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