Diaphragm plasticity in aging and disease: therapies for muscle weakness go from strength to strength

Greising, Sarah M.; Ottenheijm, Coen A.C.; O’Halloran, Ken D.; Barreiro, Esther

doi:10.1152/japplphysiol.01059.2017

Cited by 27 publications

(24 citation statements)

References 99 publications

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“…and the presence of comorbidities, among which respiratory diseases and associated circumstances (e.g. hypoxia, systemic inflammation, oxidative stress) [3,4] can be found (figure 2). All these factors can condition a greater or lesser degree of structural and functional changes, leading to a reduction in the subject's physiological capacity, and potentially to disability, frailty, loss of independence and a marked impairment in the quality of life [3].…”

Section: Ageingmentioning

confidence: 99%

Respiratory muscle senescence in ageing and chronic lung diseases

et al. 2020

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Ageing is a progressive condition that usually leads to the loss of physiological properties. This process is also present in respiratory muscles, which are affected by both senescent changes occurring in the whole organism and those that are more specific for muscles. The mechanisms of the latter changes include oxidative stress, decrease in neurotrophic factors and DNA abnormalities. Ageing normally coexists with comorbidities, including respiratory diseases, which further deteriorate the structure and function of respiratory muscles. In this context, changes intrinsic to ageing become enhanced by more specific factors such as the impairment in lung mechanics and gas exchange, exacerbations and hypoxia. Hypoxia in particular has a direct effect on muscles, mainly through the expression of inducible factors (hypoxic-inducible factor), and can result in oxidative stress and changes in DNA, decrease in mitochondrial biogenesis and defects in the tissue repair mechanisms. Intense exercise can also cause damage in respiratory muscles of elderly respiratory patients, but this can be followed by tissue repair and remodelling. However, ageing interferes with muscle repair by tampering with the function of satellite cells, mainly due to oxidative stress, DNA damage and epigenetic mechanisms. In addition to the normal process of ageing, stress-induced premature senescence can also occur, involving changes in the expression of multiple genes but without modifications in telomere length.

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Section: Ageingmentioning

confidence: 99%

Respiratory muscle senescence in ageing and chronic lung diseases

et al. 2020

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“…In the US, there are about 48 million inhabitants over 65 years of age. A statistical projection predicts that there will be about 88 million elderly citizens in 2050 in the US [2]. It is believed that the number of elderly people will be higher than the number of children born in the United States by 2030 [3].…”

Section: Introductionmentioning

confidence: 99%

Ageing of the Diaphragm Muscle

Bordoni¹,

Bruno²,

Simonelli³

2020

Cureus

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“…Respiratory muscle weakness develops in many clinical conditions, such as acute critical illness, chronic cardiopulmonary disorders, and in aging (23). In particular, impairments to the main muscle of respiration, the diaphragm, contributes substantially to pulmonary complications and poor clinical outcomes in patients (18,33).…”

Section: Introductionmentioning

confidence: 99%

Skeletal myofiber VEGF deficiency leads to mitochondrial, structural, and contractile alterations in mouse diaphragm

Cannon

Rodewohl

Adams

et al. 2019

Journal of Applied Physiology

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Respiratory muscle weakness is a hallmark of COPD, heart failure, and critical illness. Vascular endothelial growth factor (VEGF) may be an important therapeutic target in chronic cardiopulmonary disease as it is essential for neovascularization and vessel repair following trauma. We hypothesized that respiratory muscle, which is required to persistently function, would exhibit impaired mitochondrial, structural, and contractile function in skeletal myofiber VEGF gene deleted mice. We measured diaphragm biochemistry, structure, and contractile function in adult mice with conditional deletion of the VEGF‐A gene in skeletal myofibers (SkmVEGF−/−). Male SkmVEGF−/− mice (n=12) were compared to wild type (WT) controls (n=13) – both on a C57BL/6J background. Fiber bundles were isolated and electrically stimulated in vitro to evaluate force‐frequency and fatigue profiles. Mitochondrial O2 consumption and H2O2 flux (index of mitochondrial ROS) were simultaneously measured in saponin‐permeabilized fiber bundles (Oroboros, Innsbruck, AT). Fiber structure and biochemistry were measured using standard techniques (IHC, Western, ELISA). Diaphragm VEGF protein was lower in SkmVEGF−/− than WT mice (1.5±0.2 vs. 3.0±0.4 pg/total protein, p<0.05). Compared to WT mice, the force‐frequency relationship was depressed in SkmVEGF−/− (F[7,161]=15.0, p<0.05), with maximal specific force reduced by ~10 % (24±1 vs. 21±1 N/cm2; p<0.05). However, fatigue resistance tended to be greater following SkmVEGF−/− (F[2,115]=3.3, p=0.06). Fiber type proportions were unchanged, but type I fiber cross‐sectional area was reduced in SkmVEGF−/− (653±45 vs 493±53 μm2; p<0.05). Compared to WT, sarcomeric actin protein expression was reduced by ~30% in SkmVEGF−/− (p<0.05) while myosin heavy chain, MAFbx, MuRF1, PGC1α, and HIF1α protein remained unchanged (p>0.05). Mitochondrial respiration was not different between SkmVEGF−/− and WT (F[1,80]=0.9, p>0.05) in each of the respiratory states. However, H2O2 flux was reduced in SkmVEGF−/− (F[1,75]=14.6, p<0.05). Skeletal myofiber‐specific VEGF deletion contributed to diaphragm weakness, but tended to improve fatigue resistance in this highly oxidative muscle. Reductions in oxidative fiber size, sarcomeric actin protein content, and ROS generation following VEGF gene deletion may contribute to protecting mitochondrial respiratory function in the diaphragm. The adaptations may be part of compensatory mechanisms mitigating larger deficits in force generation and fatigue resistance. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Diaphragm plasticity in aging and disease: therapies for muscle weakness go from strength to strength

Cited by 27 publications

References 99 publications

Respiratory muscle senescence in ageing and chronic lung diseases

Respiratory muscle senescence in ageing and chronic lung diseases

Ageing of the Diaphragm Muscle

Skeletal myofiber VEGF deficiency leads to mitochondrial, structural, and contractile alterations in mouse diaphragm

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