Lifelong Exercise in Age Rats Improves Skeletal Muscle Function and MicroRNA Profile

Gao, Hao-En; Li, Fanghui; Xie, Tian; Ma, Song; Qiao, Yi-Bo; Wu, Da-Shuai; Sun, Lei

doi:10.1249/mss.0000000000002661

Cited by 14 publications

(15 citation statements)

References 33 publications

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“…Inhibition of PTEN improved muscle function in Duchenne muscular dystrophy [ 33 ], and aerobic exercise had a negative effect on the expression of PTEN in mice [ 34 ]. Just recently, moderate training in rats was shown to block expression of PTEN, and it was discussed that thereby an age-related loss of muscle mass might be blocked on the level of the PI3K pathway [ 35 , 36 ]. Training also activated the p38 MAPK in the muscle of rats [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Just recently, moderate training in rats was shown to block expression of PTEN, and it was discussed that thereby an age-related loss of muscle mass might be blocked on the level of the PI3K pathway [ 35 , 36 ]. Training also activated the p38 MAPK in the muscle of rats [ 36 ]. We identified activation of both PI3K and p38 MAPK in trained DUC mice but not in trained DUhTP mice, although we did not observe altered expression or activity of PTEN in response to exercise in our experimental system.…”

Section: Discussionmentioning

confidence: 99%

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Central Suppression of the GH/IGF Axis and Abrogation of Exercise-Related mTORC1/2 Activation in the Muscle of Phenotype-Selected Male Marathon Mice (DUhTP)

Brenmoehl

Walz

Caffier

et al. 2021

Cells

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The somatotropic axis is required for a number of biological processes, including growth, metabolism, and aging. Due to its central effects on growth and metabolism and with respect to its positive effects on muscle mass, regulation of the GH/IGF-system during endurance exercise is of particular interest. In order to study the control of gene expression and adaptation related to physical performance, we used a non-inbred mouse model, phenotype-selected for high running performance (DUhTP). Gene expression of the GH/IGF-system and related signaling cascades were studied in the pituitary gland and muscle of sedentary males of marathon and unselected control mice. In addition, the effects of three weeks of endurance exercise were assessed in both genetic groups. In pituitary glands from DUhTP mice, reduced expression of Pou1f1 (p = 0.002) was accompanied by non-significant reductions of Gh mRNA (p = 0.066). In addition, mRNA expression of Ghsr and Sstr2 were significantly reduced in the pituitary glands from DUhTP mice (p ≤ 0.05). Central downregulation of Pou1f1 expression was accompanied by reduced serum concentrations of IGF1 and coordinated downregulation of multiple GH/IGF-signaling compounds in muscle (e.g., Ghr, Igf1, Igf1r, Igf2r, Irs1, Irs2, Akt3, Gskb, Pik3ca/b/a2, Pten, Rictor, Rptor, Tsc1, Mtor; p ≤ 0.05). In response to exercise, the expression of Igfbp3, Igfbp 4, and Igfbp 6 and Stc2 mRNA was increased in the muscle of DUhTP mice (p ≤ 0.05). Training-induced specific activation of AKT, S6K, and p38 MAPK was found in muscles from control mice but not in DUhTP mice (p ≤ 0.05), indicating a lack of mTORC1 and mTORC2 activation in marathon mice in response to physical exercise. While hormone-dependent mTORC1 and mTORC2 pathways in marathon mice were repressed, robust increases of Ragulator complex compounds (p ≤ 0.001) and elevated sirtuin 2 to 6 mRNA expression were observed in the DUhTP marathon mouse model (p ≤ 0.05). Activation of AMPK was not observed under the experimental conditions of the present study. Our results describe coordinated downregulation of the somatotropic pathway in long-term selected marathon mice (DUhTP), possibly via the pituitary gland and muscle interaction. Our results, for the first time, demonstrate that GH/IGF effects are repressed in a context of superior running performance in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Central Suppression of the GH/IGF Axis and Abrogation of Exercise-Related mTORC1/2 Activation in the Muscle of Phenotype-Selected Male Marathon Mice (DUhTP)

Brenmoehl

Walz

Caffier

et al. 2021

Cells

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“…However, the findings of studies investigating these miRs after exercise are inconsistent. In one study, 14 days of exercise training caused no change in muscle miR29a in humans [63], nor did endurance exercise in rats alter miR 23a or 29a levels in skeletal muscle [64]. Conversely, another study found an increase in plasma miR29a in humans immediately after the completion of a marathon [65], and patients with Type 2 Diabetes Mellitus, who are at higher risk of kidney damage, had increased basal levels of miR29a in the muscle [66].…”

Section: Micro Rnamentioning

confidence: 99%

Skeletal Muscle and Kidney Crosstalk in Chronic Kidney Disease

Jenkin

Perry

2022

Cell Physiol Biochem

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The functioning of complex organisms requires a constant and delicate balance of processes both between and within cells, tissues, and organ systems. There is growing appreciation for the role of signalling crosstalk connecting different organ systems of the body, even from tissues traditionally classified as "inert" in terms of their capacity to produce chemical signals that can act on other organ systems. Many of these secreted molecules have been shown to contribute to, or exacerbate, a variety of functions and diseases in other organ systems, even if the two organs are not functionally linked. For example, there is a strong association with skeletal muscle atrophy and dysfunction in patients with chronic kidney disease (CKD). Identification of molecules produced and secreted by skeletal muscle has existed for some time, and there is emerging evidence that skeletal muscle may directly affect kidney function. Conversely, factors produced and secreted by the kidneys in various models of CKD have been shown to contribute to reduced muscle functionality. This review will focus on crosstalk in both directions between skeletal muscle and the kidneys. The emphasis will be on direct interaction between these organs using examples of secreted factors that are produced by the muscle or kidneys (including activin A, myostatin, microRNA's, irisin and mitsugumin 53), often under pathophysiological conditions. Our understanding of how the kidneys and skeletal muscle interact with each other is key to elucidating the pathophysiology processes that drive health and disease.

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“…Thus, the AKT/PTEN pathway is critical for skeletal muscle hypertrophy and prevention of muscle atrophy 17 . Our previous studies have shown that lifelong exercise‐activated PTEN/AKT pathway and indirectly inhibited the HIPPO pathway activation 18 . Therefore, we investigated whether HIIT acts on HIPPO pathway to prevent muscle atrophy along with regulating AKT/PTEN pathway.…”

Section: Introductionmentioning

confidence: 99%

“…17 Our previous studies have shown that lifelong exercise-activated PTEN/AKT pathway and indirectly inhibited the HIPPO pathway activation. 18 Therefore, we investigated whether HIIT acts on HIPPO pathway to prevent muscle atrophy along with regulating AKT/PTEN pathway. Additionally, exerciseinduced constriction modified the expression of multiple miRNAs in human skeletal muscle, including miR-1, miR-133a, miR-133b, miR-378a, and miR-486.…”

Section: Introductionmentioning

confidence: 99%

Indirect regulation of HIPPO pathway by miRNA mediates high‐intensity intermittent exercise to ameliorate aging skeletal muscle function

Wang

et al. 2023

Scandinavian Med Sci Sports

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Exercise‐induced microRNA (miRNA) and HIPPO pathways participate in the regulation of skeletal muscle plasticity but their underlying mechanisms remain unclear. We aimed to investigate the effect of high‐intensity interval training (HIIT) on miRNA expression and the HIPPO pathway in the skeletal muscle of aging rats to determine its role in the amelioration of muscle aging. Thirty‐six 18‐month‐old female rats were randomly divided into sedentary control (SED, n = 12), moderate‐intensity continuous training (MICT, n = 12), and HIIT (n = 12) groups, with continuous exercise for 8 months. Quantitative reverse transcription‐polymerase chain reaction, immunoblotting, KEGG enrichment, and dual‐luciferase assays were performed on the target skeletal muscle. Compared with the SED group, the MICT and HIIT groups showed a significant trend of improvement in Lee's index and grip strength and a marked increase in skeletal muscle mitochondrial function, apoptosis, antioxidant, and lipolysis‐related protein expression. They also exhibited PI3K/AKT pathway activation and a decrease in expression of HIPPO pathway‐related proteins; 20 miRNAs were differentially expressed and enriched in the exercise group compared with the SED group, including the HIPPO pathway and metabolic pathways. Further analysis of L6 cells confirmed that miR‐182 may target PTEN, which indirectly regulates HIPPO signaling, but not Mob1. the combined application of HIIT and MICT increased the antioxidant and lipolytic capacities of skeletal muscle and improved atrophy of aging skeletal muscle; HIIT was more effective than MICT. This may be related to HIIT‐mediated AKT pathway activation and HIPPO pathway inhibition by miRNAs (miR‐486 and miR‐182).

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Lifelong Exercise in Age Rats Improves Skeletal Muscle Function and MicroRNA Profile

Abstract: Supplemental digital content is available in the text.

Cited by 14 publications

References 33 publications

Central Suppression of the GH/IGF Axis and Abrogation of Exercise-Related mTORC1/2 Activation in the Muscle of Phenotype-Selected Male Marathon Mice (DUhTP)

Central Suppression of the GH/IGF Axis and Abrogation of Exercise-Related mTORC1/2 Activation in the Muscle of Phenotype-Selected Male Marathon Mice (DUhTP)

Skeletal Muscle and Kidney Crosstalk in Chronic Kidney Disease

Indirect regulation of HIPPO pathway by miRNA mediates high‐intensity intermittent exercise to ameliorate aging skeletal muscle function

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