The molecular athlete: exercise physiology from mechanisms to medals

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(3), P. 1693 - 1787

Published: Jan. 5, 2023

Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels endurance strength elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding signal integration, interpretation, output coordination cellular molecular mechanisms that govern plasticity across this continuum is incomplete. As such, training methods their application largely rely on “trial-and-error” approach, experience practices successful coaches often providing bases for “post hoc” scientific enquiry research. This review provides synopsis morphological functional changes along underlying adaptation endurance- resistance-based training. These traits are placed in context innate genetic interindividual differences performance, special consideration given aging athletes. Collectively, we provide comprehensive overview response different modes how such adaptations translate “molecules medals.”

Language: Английский

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Adaptive Responses to Hypoxia and/or Hyperoxia in Humans

Antioxidants and Redox Signaling, Journal Year: 2022, Volume and Issue: 37(13-15), P. 887 - 912

Published: Feb. 1, 2022

Significance: Oxygen is indispensable for aerobic life, but its utilization exposes cells and tissues to oxidative stress; thus, tight regulation of cellular, tissue, systemic oxygen concentrations crucial. Here, we review the current understanding how human organism (mal-)adapts low (hypoxia) high (hyperoxia) levels these adaptations may be harnessed as therapeutic or performance enhancing strategies at level. Recent Advances: Hyperbaric therapy already a cornerstone modern medicine, application mild hypoxia, that is, hypoxia conditioning (HC), strengthen resilience organs whole body severe hypoxic insults an important preparation high-altitude sojourns protect cardiovascular system from hypoxic/ischemic damage. Many other applications hypo- and/or hyperoxia are only just emerging. HC-sometimes in combination with hyperoxic interventions-is gaining traction treatment chronic diseases, including numerous neurological disorders, enhancement. Critical Issues: The dose- intensity-dependent effects varying render hypoxia- hyperoxia-based interventions potentially highly beneficial, yet hazardous, although risks versus benefits ill-defined. Future Directions: field expanding rapidly, novel increasingly recognized, example, modulation aging processes, mood metabolic diseases. To advance hypoxia/hyperoxia clinical applications, more research on intensity, duration, frequency altered concentrations, well individual vulnerabilities such interventions, paramount. Antioxid. Redox Signal. 37, 887-912.

Language: Английский

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Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 1, 2022

Abstract Angiotensin-converting enzyme 2 (ACE2) has proven beneficial in attenuating diabetic cardiomyopathy (DCM) but been found to be a substrate of disintegrin and metalloprotease protein-17 (ADAM17). However, whether ADAM17 plays role the pathogenesis intervention DCM is obscure. In this study, we created cardiomyocyte-specific knockout (A17 α-MHCKO ) mice, left ventricular dimension, function, pathology molecular biology were assessed fl/fl control, A17 mice. Both differentiated H9c2 cells neonatal rat cardiomyocytes (NRCMs) used explore mechanisms underlying effect on DCM. The results showed that protein expression activity upregulated whereas ACE2 was downregulated myocardium Cardiomyocyte-specific mitigated cardiac fibrosis cardiomyocyte apoptosis ameliorated dysfunction mice with Bioinformatic analyses detected number genes enriched metabolic pathways, particular AMPK signaling pathway, expressed differentially between hearts mechanism may involve activated increased autophagosome formation improved autophagic flux, which reduced apoptotic response cardiomyocytes. addition, hypoxia-inducible factor-1α (HIF-1α) might act as an upstream mediator affect via α1 A-adrenergic receptor (ADRA1A). These indicated shedding enhanced DCM, reversed by knockout. Thus, inhibition provide promising approach treatment

Language: Английский

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Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(11), P. 1049 - 1082

Published: Oct. 20, 2022

Reversible, spatial, and temporal regulation of metabolic reprogramming epigenetic homeostasis are prominent hallmarks carcinogenesis. Cancer cells reprogram their metabolism to meet the high bioenergetic biosynthetic demands for vigorous proliferation. Epigenetic dysregulation is a common feature human cancers, which contributes tumorigenesis maintenance malignant phenotypes by regulating gene expression. The epigenome sensitive changes. Metabolism produces various metabolites that substrates, cofactors, or inhibitors enzymes. Alterations in pathways fluctuations intermediate convey information regarding intracellular status into nucleus modulating activity enzymes thus remodeling landscape, inducing transcriptional responses heterogeneous requirements. regulated machinery at both post-transcriptional levels. modifiers, chromatin remodelers non-coding RNAs integral contributors regulatory networks involved cancer metabolism, facilitating transformation. However, significance close connection between epigenetics context has not been fully deciphered. Thus, it will be constructive summarize update emerging new evidence supporting this bidirectional crosstalk deeply assess how abnormalities could exploited optimize treatment paradigms establish therapeutic options. In review, we central mechanisms reciprocally modulate each other elaborate upon major contributions interplays aberrations rewiring initiation development. Finally, highlight potential opportunities hematological malignancies solid tumors targeting epigenetic-metabolic circuit. summary, endeavored depict current understanding coordination these fundamental more comprehensively provide perspectives utilizing targets treatment.

Language: Английский

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Molecular Mechanisms of High-Altitude Acclimatization

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1698 - 1698

Published: Jan. 15, 2023

High-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms affect appropriate acclimatization hypobaric and/or normobaric hypoxia and curtail the development of HAIs. The understanding these is essential optimize hypoxic for efficient prophylaxis treatment This review aims link outcomes either adverse effects high-altitude/hypoxia or developing tolerance with acclimatization. After summarizing systemic physiological responses high-altitude exposure, associated acclimatization, epidemiology pathophysiology various HAIs, article focuses on adjustments maladjustments during Pivotal modifying include orchestrated by transcription factors, most notably inducible reciprocal mitochondrial functions REDOX homeostasis. In addition, discussed are genetic factors resultant proteomic profiles determining hypoxia-modifying culminating in successful Lastly, discusses practical considerations related aspects altitude training strategies.

Language: Английский

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