Dataset Information

Skeletal Muscle Mitochondrial Function and Fatigability in Older Adults.

ABSTRACT: Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults.The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 ± 5.0 years (47% female, 93% white), with a body mass index of 25.9 ± 2.7 kg/m(2) and usual gait-speed of 1.2 ± 0.2 m/s. Fatigability was defined using rating of perceived exertion (6-20 point Borg scale) after a 5-minute treadmill walk at 0.72 m/s. Phosphocreatine recovery in the quadriceps was measured using (31)P magnetic resonance spectroscopy and images of the quadriceps were captured to calculate quadriceps volume. ATPmax (mM ATP/s) and oxidative capacity of the quadriceps (ATPmax·Quadriceps volume) were calculated. Peak aerobic capacity (VO2peak) was measured using a modified Balke protocol.ATPmax·Quadriceps volume was associated with VO2peak and was 162.61mM ATP·mL/s lower (p = .03) in those with high (rating of perceived exertion ?10) versus low (rating of perceived exertion ?9) fatigability. Participants with high fatigability required a significantly higher proportion of VO2peak to walk at 0.72 m/s compared with those with low fatigability (58.7 ± 19.4% vs 44.9 ± 13.2%, p < .05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability (odds ratio: 0.34, 95% CI: 0.11-1.01, p = .05).Lower capacity for oxidative phosphorylation in the quadriceps, perhaps by contributing to lower VO2peak, is associated with higher fatigability in older adults.

SUBMITTER: Santanasto AJ

PROVIDER: S-EPMC4612379 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Skeletal Muscle Mitochondrial Function and Fatigability in Older Adults.

Santanasto Adam J AJ Glynn Nancy W NW Jubrias Sharon A SA Conley Kevin E KE Boudreau Robert M RM Amati Francesca F Mackey Dawn C DC Simonsick Eleanor M EM Strotmeyer Elsa S ES Coen Paul M PM Goodpaster Bret H BH Newman Anne B AB

The journals of gerontology. Series A, Biological sciences and medical sciences 20140828 11

<h4>Background</h4>Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults.<h4>Methods</h4>The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 ± 5.0 years (47% female, 93% white), with a body mass index of 25.9 ± 2.7 kg/m(2) and usual gait-speed of 1.2 ± 0.2 m/ ...[more]

PMID: 25167867

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Project description:NEW FINDINGS:What is the central question of this study? Interleukin-6 has been associated with muscle mass and metabolism in both physiological and pathological conditions. A causal role for interleukin-6 in the induction of fatigue and disruption of mitochondrial function has not been determined. What is the main finding and its importance? We demonstrate that chronically elevated interleukin-6 increased skeletal muscle fatigability and disrupted mitochondrial content and function independent of changes in fibre type and mass. ABSTRACT:Interleukin-6 (IL-6) can initiate intracellular signalling in skeletal muscle by binding to the IL-6-receptor and interacting with the transmembrane gp130 protein. Circulating IL-6 has established effects on skeletal muscle mass and metabolism in both physiological and pathological conditions. However, the effects of circulating IL-6 on skeletal muscle function are not well understood. The purpose of this study was to determine whether chronically elevated systemic IL-6 was sufficient to disrupt skeletal muscle force, fatigue and mitochondrial function. Additionally, we examined the role of muscle gp130 signalling during overexpression of IL-6. Systemic IL-6 overexpression for 2 weeks was achieved by electroporation of an IL-6 overexpression plasmid or empty vector into the quadriceps of either C57BL/6 (WT) or skeletal muscle gp130 knockout (KO) male mice. Tibialis anterior muscle in situ functional properties and mitochondrial respiration were determined. Interleukin-6 accelerated in situ skeletal muscle fatigue in the WT, with a 18.5% reduction in force within 90 s of repeated submaximal contractions and a 7% reduction in maximal tetanic force after 5 min. There was no difference between fatigue in the KO and KO+IL-6. Interleukin-6 reduced WT muscle mitochondrial respiratory control ratio by 36% and cytochrome c oxidase activity by 42%. Interleukin-6 had no effect on either KO respiratory control ratio or cytochrome c oxidase activity. Interleukin-6 also had no effect on body weight, muscle mass or tetanic force in either genotype. These results provide evidence that 2 weeks of elevated systemic IL-6 is sufficient to increase skeletal muscle fatigability and decrease muscle mitochondrial content and function, and these effects require muscle gp130 signalling.

Project description:BackgroundBoosting NAD+ via supplementation with niacin equivalents has been proposed as a potential modality capable of promoting healthy aging and negating age-dependent declines of skeletal muscle mass and function.ObjectivesWe investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skeletal muscle mitochondrial function in physically compromised older adults.MethodsA randomized, double-blind, controlled trial was conducted in 14 (female/male: 4/10) community-dwelling, older adults with impaired physical function [age, 72.9 ± 4.0 years; BMI, 25.2 ± 2.3 kg/m2]. Participants were supplemented with 207.5 mg niacin equivalents/day [intervention (INT)] and a control product (CON) that did not contain niacin equivalents, each for 32 days. The primary outcomes tested were mitochondrial oxidative capacity and exercise efficiency, analyzed by means of paired Student's t-tests. Secondary outcomes, such as NAD+ concentrations, were analyzed accordingly.ResultsFollowing supplementation, skeletal muscle NAD+ concentrations [7.5 ± 1.9 compared with 7.9 ± 1.6 AU, respectively] in INT compared with CON conditions were not significantly different compared to the control condition, whereas skeletal muscle methyl-nicotinamide levels were significantly higher under NAD+-precursor supplementation [INT, 0.098 ± 0.063 compared with CON, 0.025 ± 0.014; P = 0.001], suggesting an increased NAD+ metabolism. Conversely, neither ADP-stimulated [INT, 82.1 ± 19.0 compared with CON, 84.0 ± 19.2; P = 0.716] nor maximally uncoupled mitochondrial respiration [INT, 103.4 ± 30.7 compared with CON, 108.7 ± 33.4; P = 0.495] improved under NAD+-precursor supplementation, nor did net exercise efficiency during the submaximal cycling test [INT, 20.2 ± 2.77 compared with CON, 20.8 ± 2.88; P = 0.342].ConclusionsOur findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function. This study was registered at clinicaltrials.gov as NCT03310034.

Dataset Information

Skeletal Muscle Mitochondrial Function and Fatigability in Older Adults.

Publications

Skeletal Muscle Mitochondrial Function and Fatigability in Older Adults.

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