Influence of anaerobic and aerobic exercise on age-related pathways in skeletal muscle

Navas-Enamorado, Ignacio; Bernier, Michel; Brea-Calvo, Gloria; Cabo, Rafael de

doi:10.1016/j.arr.2017.04.005

Cited by 18 publications

(16 citation statements)

References 247 publications

(270 reference statements)

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“…Skeletal muscle strength and contractile function is intimately linked to health span and organismal survival . In line with this, the rapid lethality of PCKO mice is paralleled by profound impairments in grip strength, neuromuscular function, and ability to move, which at the muscle level presents as an ~85–95% reduction in intrinsic force production.…”

Section: Discussionmentioning

confidence: 91%

p300 and cAMP response element‐binding protein‐binding protein in skeletal muscle homeostasis, contractile function, and survival

Svensson

LaBarge

Sathe

et al. 2020

J cachexia sarcopenia muscle

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Background Reversible ε-amino acetylation of lysine residues regulates transcription as well as metabolic flux; however, roles for specific lysine acetyltransferases in skeletal muscle physiology and function are unknown. In this study, we investigated the role of the related acetyltransferases p300 and cAMP response element-binding protein-binding protein (CBP) in skeletal muscle transcriptional homeostasis and physiology in adult mice. Methods Mice with skeletal muscle-specific and inducible knockout of p300 and CBP (PCKO) were generated by crossing mice with a tamoxifen-inducible Cre recombinase expressed under the human α-skeletal actin promoter with mice having LoxP sites flanking exon 9 of the Ep300 and Crebbp genes. Knockout of PCKO was induced at 13-15 weeks of age via oral gavage of tamoxifen for 5 days to both PCKO and littermate control [wildtype (WT)] mice. Body composition, food intake, and muscle function were assessed on day 0 (D0) through 5 (D5). Microarray and tandem mass tag mass spectrometry analyses were performed to assess global RNA and protein levels in skeletal muscle of PCKO and WT mice.Results At D5 after initiating tamoxifen treatment, there was a reduction in body weight (À15%), food intake (À78%), stride length (À46%), and grip strength (À45%) in PCKO compared with WT mice. Additionally, ex vivo contractile function [tetanic tension (kPa)] was severely impaired in PCKO vs. WT mice at D3 (~70-80% lower) and D5 (~80-95% lower) and resulted in lethality within 1 week-a phenotype that is reversed by the presence of a single allele of either p300 or CBP. The impaired muscle function in PCKO mice was paralleled by substantial transcriptional alterations (3310 genes; false discovery rate < 0.1), especially in gene networks central to muscle contraction and structural integrity. This transcriptional uncoupling was accompanied by changes in protein expression patterns indicative of impaired muscle function, albeit to a smaller magnitude (446 proteins; fold-change > 1.25; false discovery rate < 0.1). Conclusions These data reveal that p300 and CBP are required for the control and maintenance of contractile function and transcriptional homeostasis in skeletal muscle and, ultimately, organism survival. By extension, modulating p300/CBP function may hold promise for the treatment of disorders characterized by impaired contractile function in humans.

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Section: Discussionmentioning

confidence: 91%

p300 and cAMP response element‐binding protein‐binding protein in skeletal muscle homeostasis, contractile function, and survival

Svensson

LaBarge

Sathe

et al. 2020

J cachexia sarcopenia muscle

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“…Skeletal muscle adaptations to CR and exercise lead to enhanced capacity for glucose utilization and FA oxidation (Navas‐Enamorado, Bernier, Brea‐Calvo & de Cabo, 2017). Despite the lack of effects on peripheral glucose homeostasis, bioenergetic efficiency in skeletal muscle was improved in response to overexpression of CYB5R3 and NQO1, mirroring a CR‐like metabolic profile that was accompanied by enhanced muscle strength, motor coordination, and balance.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

et al. 2018

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SummaryCalorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b 5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through upregulation of these NADH‐dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and, importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD +/sirtuin pathway. The results highlight the importance of these NAD + producers for the promotion of health and extended lifespan.

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“…Thus, muscle fibers containing high mitochondrial content are more resistant to the development of fatigue compared to muscle fibers with lower mitochondrial content (Pette, 1985 ; Casey et al, 1996 ). Mitochondrial biogenesis can be induced in skeletal muscle by stimuli such as repeated muscle contractions, and increases in mitochondrial content and function contribute to aerobic adaptations observed during exercise training (Ryan et al, 2013b ; Hood et al, 2015 ; Navas-Enamorado et al, 2017 ). Alternatively, muscle disuse and pathology can result in mitochondrial dysfunction, and declines in mitochondrial content and/or function have been implicated in symptoms associated many neurological and cardiovascular diseases (Kent-Braun et al, 1994a , 1997 ; Vorgerd et al, 2000 ; Morino et al, 2005 ; Koves et al, 2008 ; McCully et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Assessment of Mitochondrial Dysfunction in Clinical Populations Using Near-Infrared Spectroscopy

Willingham

McCully

2017

Front. Physiol.

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The ability to sustain submaximal exercise is largely dependent on the oxidative capacity of mitochondria within skeletal muscle, and impairments in oxidative metabolism have been implicated in many neurologic and cardiovascular pathologies. Here we review studies which have demonstrated the utility of Near-infrared spectroscopy (NIRS) as a method of evaluating of skeletal muscle mitochondrial dysfunction in clinical human populations. NIRS has been previously used to noninvasively measure tissue oxygen saturation, but recent studies have demonstrated the utility of NIRS as a method of evaluating skeletal muscle oxidative capacity using post-exercise recovery kinetics of oxygen metabolism. In comparison to historical methods of measuring muscle metabolic dysfunction in vivo, NIRS provides a more versatile and economical method of evaluating mitochondrial oxidative capacity in humans. These advantages generate great potential for the clinical applicability of NIRS as a means of evaluating muscle dysfunction in clinical populations.

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Influence of anaerobic and aerobic exercise on age-related pathways in skeletal muscle

Cited by 18 publications

References 247 publications

p300 and cAMP response element‐binding protein‐binding protein in skeletal muscle homeostasis, contractile function, and survival

p300 and cAMP response element‐binding protein‐binding protein in skeletal muscle homeostasis, contractile function, and survival

Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction

In Vivo Assessment of Mitochondrial Dysfunction in Clinical Populations Using Near-Infrared Spectroscopy

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Influence of anaerobic and aerobic exercise on age-related pathways in skeletal muscle

Cited by 18 publications

References 247 publications

p300 and cAMP response element‐binding protein‐binding protein in skeletal muscle homeostasis, contractile function, and survival

p300 and cAMP response element‐binding protein‐binding protein in skeletal muscle homeostasis, contractile function, and survival

Overexpression of CYB5R3 and NQO1, two NAD+‐producing enzymes, mimics aspects of caloric restriction

In Vivo Assessment of Mitochondrial Dysfunction in Clinical Populations Using Near-Infrared Spectroscopy

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Overexpression of CYB5R3 and NQO1, two NAD⁺‐producing enzymes, mimics aspects of caloric restriction