The Akt/mTOR pathway: Data comparing young and aged mice with leucine supplementation at the onset of skeletal muscle regeneration

Perry, Richard; Brown, Lemuel A.; Lee, David E.; Brown, Jacob L.; Baum, Joseph D.; Greene, Nicholas P.; Washington, Tyrone A.

doi:10.1016/j.dib.2016.08.013

Cited by 12 publications

(24 citation statements)

References 7 publications

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Section: Resultsmentioning

confidence: 99%

“…Expression of relative mTOR did not change with age, however, content of phosphorylated and total mTOR levels were 79% and 76% lower (p < 0.05), respectively, in the aged mice [see Figure 1B, 1E in (Perry et al, 2016)]. Aged mice had a 52% decreased expression of relative p70S6K [p < 0.05; see Figure 1C in (Perry et al, 2016)] compared to young mice. Content level of p-p70S6K did not change with age, but total p70S6K content was 48% higher in the aged animals compared to the young mice [p < 0.05; see Figure in 1E in (Perry et al, 2016)].…”

Section: Resultsmentioning

confidence: 99%

“…Content level of p-p70S6K did not change with age, but total p70S6K content was 48% higher in the aged animals compared to the young mice [p < 0.05; see Figure in 1E in (Perry et al, 2016)]. In aged mice, expression of relative 4EBP-1 was 16% lower [p < 0.05; see Figure 1D in (Perry et al, 2016)] compared to young mice. However, levels of p-4EBP and total 4EBP were 140% and 184% higher (p < 0.05), respectively, in aged mice compared to young mice [see Figure 1E in (Perry et al, 2016)].…”

Section: Resultsmentioning

confidence: 99%

“…Age had no effect on expression levels of relative, phosphorylated or total Akt [see Figure 1A, 1E in (Perry et al, 2016)]. Expression of relative mTOR did not change with age, however, content of phosphorylated and total mTOR levels were 79% and 76% lower (p < 0.05), respectively, in the aged mice [see Figure 1B, 1E in (Perry et al, 2016)].…”

Section: Resultsmentioning

confidence: 99%

“…Aged mice had a 52% decreased expression of relative p70S6K [p < 0.05; see Figure 1C in (Perry et al, 2016)] compared to young mice. Content level of p-p70S6K did not change with age, but total p70S6K content was 48% higher in the aged animals compared to the young mice [p < 0.05; see Figure in 1E in (Perry et al, 2016)]. In aged mice, expression of relative 4EBP-1 was 16% lower [p < 0.05; see Figure 1D in (Perry et al, 2016)] compared to young mice.…”

Section: Resultsmentioning

confidence: 99%

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Differential effects of leucine supplementation in young and aged mice at the onset of skeletal muscle regeneration

Perry

Brown

Lee

et al. 2016

Mechanisms of Ageing and Development

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Aging decreases the ability of skeletal muscle to respond to injury. Leucine has been demonstrated to target protein synthetic pathways in skeletal muscle thereby enhancing this response. However, the effect of aging on leucine-induced alterations in protein synthesis at the onset of skeletal muscle regeneration has not been fully elucidated. The purpose of this study was to determine if aging alters skeletal muscle regeneration and leucine-induced alterations in markers of protein synthesis. The tibialis anterior of young (3 months) and aged (24 months) female C57BL/6J mice were injected with either bupivacaine or PBS, and the mice were given ad libitum access to leucine-supplemented or normal drinking water. Protein and gene expression of markers of protein synthesis and degradation, respectively, were analyzed at three days post-injection. Following injury in young mice, leucine supplementation was observed to elevate only p-p70S6K. In aged mice, leucine was shown to elicit higher p-mTOR content with and without injury, and p-4EBP-1 content post-injury. Additionally in aged mice, leucine was shown to elicit higher content of relative p70S6K post-injury. Our study shows that leucine supplementation affects markers of protein synthesis at the onset of skeletal muscle regeneration differentially in young and aged mice.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Differential effects of leucine supplementation in young and aged mice at the onset of skeletal muscle regeneration

Perry

Brown

Lee

et al. 2016

Mechanisms of Ageing and Development

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A subset of microRNAs in the Dlk1‐Dio3 cluster regulates age‐associated muscle atrophy by targeting Atrogin‐1

Shin

Kwon

Lee

et al. 2020

J cachexia sarcopenia muscle

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Background The microRNAs (miRNAs) down-regulated in aged mouse skeletal muscle were mainly clustered within the delta-like homologue 1 and the type III iodothyronine deiodinase (Dlk1-Dio3) genomic region. Although clustered miRNAs are coexpressed and regulate multiple targets in a specific signalling pathway, the function of miRNAs in the Dlk1-Dio3 cluster in muscle aging is largely unknown. We aimed to ascertain whether these miRNAs play a common role to regulate age-related muscle atrophy. Methods To examine anti-atrophic effect of miRNAs, we individually transfected 42 miRNA mimics in fully differentiated myotubes and analysed their diameters. The luciferase reporter assay using target 3′ untranslated region (UTR) and RNA pull-down assay were employed to ascertain the target predicted by the TargetScan algorithm. To investigate the therapeutic potential of the miRNAs in vivo, we generated adeno-associated virus (AAV) serotype 9 expressing green fluorescent protein (GFP) (AAV9-GFP) bearing miR-376c-3p and infected it into the tibialis anterior muscle of old mice. We performed morphometric analysis and measured ex vivo isometric force using a force transducer. Human gluteus maximus muscle tissues (ages ranging from 25 to 80 years) were used to investigate expression levels of the conserved miRNAs in the Dlk1-Dio3 cluster. Results We found that the majority of miRNAs (33 out of 42 tested) in the cluster induced anti-atrophic phenotypes in fully differentiated myotubes with increasing their diameters. Eighteen of these miRNAs, eight of which are conserved in humans, harboured predicted binding sites in the 3′ UTR of muscle atrophy gene-1 (Atrogin-1) encoding a muscle-specific E3 ligase. Direct interactions were identified between these miRNAs and the 3′ UTR of Atrogin-1, leading to repression of Atrogin-1 and thereby induction of eIF3f protein content, in both human and mouse skeletal muscle cells. Intramuscular delivery of AAV9 expressing miR-376c-3p, one of the most effective miRNAs in myotube thickening, dramatically ameliorated skeletal muscle atrophy and improved muscle function, including isometric force, twitch force, and fatigue resistance in old mice. Consistent with our findings in mice, the expression of miRNAs in the cluster was significantly down-regulated in human muscle from individuals > 50 years old.

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IBS008738, a TAZ activator, facilitates muscle repair and inhibits muscle injury in a mouse model of sport-induced injury

Wang,

Liu,

Wang

et al. 2024

Cytotechnology

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The Akt/mTOR pathway: Data comparing young and aged mice with leucine supplementation at the onset of skeletal muscle regeneration

Cited by 12 publications

References 7 publications

Differential effects of leucine supplementation in young and aged mice at the onset of skeletal muscle regeneration

Differential effects of leucine supplementation in young and aged mice at the onset of skeletal muscle regeneration

A subset of microRNAs in the Dlk1‐Dio3 cluster regulates age‐associated muscle atrophy by targeting Atrogin‐1

IBS008738, a TAZ activator, facilitates muscle repair and inhibits muscle injury in a mouse model of sport-induced injury

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