Topic Editors

Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA
Prof. Dr. Zhen Yan
Department of Medicine-Cardiovascular Medicine, University of Virginia, Charlottesville, VA, USA

Molecular Mechanisms of Exercise and Healthspan

Abstract submission deadline
closed (30 November 2023)
Manuscript submission deadline
2 November 2024
Viewed by
14906

Topic Information

Dear Colleagues,

Exercise is increasingly being recognized as a broadly effective intervention for the preservation of long-term functionality during the aging process, leading to the popularization of the phase, “exercise is medicine”. Chronic exercise lowers the risk of many age-related diseases, including diabetes, heart disease, and several forms of cancer. Exercise is also generally thought to preserve basic mobility, cognitive function, and circadian rhythms, as well as contributing to psychological health. Despite the many benefits of chronic exercise, the mechanistic requirements for these benefits to accrue are still not fully understood, and are a highly active research topic. As many patients are unable to execute demanding exercise programs, the identification of downstream mechanistic targets to pharmaceutically deliver the benefits of chronic exercise has a transformative potential for the treatment of age-related disease and the maintenance of healthy aging. In this topic, we examine recent findings in diverse model systems that increase our understanding of the molecular outputs of exercise, as well as their requirements for the myriad benefits that exercise provides. This topic will bridge several disciplines that have important contributions to make to this experimental area. These will include data from human studies, from genetic interventions in animal models, and the contribution of diet or various dietary supplements to modulate the impact of exercise. In addition to developing knowledge of how to modulate or optimize the effects of exercise, we will also collect findings related to mechanistic impact on various disease models, and findings related to systemic interactions at both the organ and cellular level.

Dr. Robert Wessells
Prof. Dr. Zhen Yan
Topic Editors

Keywords

  • exercise
  • metabolism
  • aging model systems
  • muscle
  • heart
  • adipose
  • myokine
  • nervous system
  • age-related disease

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomolecules
biomolecules
4.8 9.4 2011 16.3 Days CHF 2700 Submit
Cells
cells
5.1 9.9 2012 17.5 Days CHF 2700 Submit
International Journal of Molecular Sciences
ijms
4.9 8.1 2000 18.1 Days CHF 2900 Submit
Journal of Molecular Pathology
jmp
- - 2020 25.4 Days CHF 1000 Submit
Muscles
muscles
- - 2022 36.2 Days CHF 1000 Submit

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Published Papers (8 papers)

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22 pages, 11579 KiB  
Article
Exercise Rescues Obesogenic-Related Genes in the Female Hypothalamic Arcuate Nucleus: A Potential Role of miR-211 Modulation
by Kayla Rapps, Asaf Marco, Hilla Pe’er-Nissan, Tatiana Kisliouk, Gabrielle Stemp, Gal Yadid, Aron Weller and Noam Meiri
Int. J. Mol. Sci. 2024, 25(13), 7188; https://doi.org/10.3390/ijms25137188 - 29 Jun 2024
Viewed by 279
Abstract
Obesity is a major public health concern that is associated with negative health outcomes. Exercise and dietary restriction are commonly recommended to prevent or combat obesity. This study investigates how voluntary exercise mitigates abnormal gene expression in the hypothalamic arcuate nucleus (ARC) of [...] Read more.
Obesity is a major public health concern that is associated with negative health outcomes. Exercise and dietary restriction are commonly recommended to prevent or combat obesity. This study investigates how voluntary exercise mitigates abnormal gene expression in the hypothalamic arcuate nucleus (ARC) of diet-induced obese (DIO) rats. Using a transcriptomic approach, novel genes in the ARC affected by voluntary wheel running were assessed alongside physiology, pharmacology, and bioinformatics analysis to evaluate the role of miR-211 in reversing obesity. Exercise curbed weight gain and fat mass, and restored ARC gene expression. High-fat diet (HFD) consumption can dysregulate satiety/hunger mechanisms in the ARC. Transcriptional clusters revealed that running altered gene expression patterns, including inflammation and cellular structure genes. To uncover regulatory mechanisms governing gene expression in DIO attenuation, we explored miR-211, which is implicated in systemic inflammation. Exercise ameliorated DIO overexpression of miR-211, demonstrating its pivotal role in regulating inflammation in the ARC. Further, in vivo central administration of miR-211-mimic affected the expression of immunity and cell cycle-related genes. By cross-referencing exercise-affected and miR-211-regulated genes, potential candidates for obesity reduction through exercise were identified. This research suggests that exercise may rescue obesity through gene expression changes mediated partially through miR-211. Full article
(This article belongs to the Topic Molecular Mechanisms of Exercise and Healthspan)
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20 pages, 2271 KiB  
Article
Effects of Treadmill Running at Different Light Cycles in Mice with Metabolic Disorders
by Anna Nikolaevna Zakharova, Kseniya Gennadievna Milovanova, Anna Alekseevna Orlova, Elena Yuryevna Dyakova, Julia Gennadievna Kalinnikova, Olesya Vadimovna Kollantay, Igor Yurievich Shuvalov, Alexander Valerievich Chibalin and Leonid Vladimirovich Kapilevich
Int. J. Mol. Sci. 2023, 24(20), 15132; https://doi.org/10.3390/ijms242015132 - 13 Oct 2023
Cited by 2 | Viewed by 1554
Abstract
Type 2 diabetes mellitus accounts for about 90% of cases of diabetes and is considered one of the most important problems of our time. Despite a significant number of studies on glucose metabolism, the molecular mechanisms of its regulation in health and disease [...] Read more.
Type 2 diabetes mellitus accounts for about 90% of cases of diabetes and is considered one of the most important problems of our time. Despite a significant number of studies on glucose metabolism, the molecular mechanisms of its regulation in health and disease remain insufficiently studied. That is why non-drug treatment of metabolic disorders is of great relevance, including physical activity. Metabolic changes under the influence of physical activity are very complex and are still difficult to understand. This study aims to deepen the understanding of the effect of physical exercise on metabolic changes in mice with diabetes mellitus. We studied the effect of forced treadmill running on body weight and metabolic parameters in mice with metabolic disorders. We developed a high-fat-diet-induced diabetic model of metabolic disorders. We exposed mice to forced treadmill running for 4 weeks. We determined glucose and insulin levels in the blood plasma biochemically and analyzed Glut-4 and citrate synthase in M. gastrocnemius muscle tissue using Western blotting. The research results show that daily treadmill running has different effects on different age groups of mice with metabolic disorders. In young-age animals, forced running has a more pronounced effect on body weight. At week 12, young obese mice had a 17% decrease in body weight. Body weight did not change in old mice. Moreover, at weeks 14 and 16, the decrease in body weight was more significant in the young mice (by 17%) compared to the old mice (by 6%) (p < 0.05). In older animals, it influences the rate of glucose uptake. At 60 min, the blood glucose in the exercised older mice decreased to 14.46 mmol/L, while the glucose concentration in the non-exercised group remained at 17 mmol/L. By 120 min, in mice subjected to exercise, the blood glucose approached the initial value (6.92 mmol/L) and amounted to 8.35 mmol/L. In the non-exercised group, this difference was 45%. The effects of physical activity depend on the time of day. The greater effect is observed when performing shift training or exercise during the time when animals are passive (light phase). In young mice, light phase training had a significant effect on increasing the content of Glut-4 in muscle tissue (84.3 ± 11.3%, p < 0.05 with control group—59.3 ± 7.8%). In aged mice, shift training caused an increase in the level of Glut-4 in muscle tissue (71.3 ± 4.1%, p < 0.05 with control group—56.4 ± 10,9%). In the group of aged mice, a lower CS level was noticed in all groups in comparison with young mice. It should also be noted that we observed that CS increased during exercise in the group of young mice, especially during light phase training. The CS content in the light phase subgroup (135.8 ± 7.0%) was higher than in the dark phase subgroup (113.3 ± 7.7%) (p = 0.0006). The CS decreased in aged chow-fed mice and increased in the high-fat-fed group. The CS content in the chow diet group (58.2 ± 5.0%) was 38% lower than in the HFD group (94.9 ± 8.8%). Full article
(This article belongs to the Topic Molecular Mechanisms of Exercise and Healthspan)
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14 pages, 1408 KiB  
Article
Sedentary Behavior Impacts on the Epigenome and Transcriptome: Lessons from Muscle Inactivation in Drosophila Larvae
by Avivit Brener, Dana Lorber, Adriana Reuveny, Hila Toledano, Lilach Porat-Kuperstein, Yael Lebenthal, Eviatar Weizman, Tsviya Olender and Talila Volk
Cells 2023, 12(19), 2333; https://doi.org/10.3390/cells12192333 - 22 Sep 2023
Viewed by 1381
Abstract
The biological mechanisms linking sedentary lifestyles and metabolic derangements are incompletely understood. In this study, temporal muscle inactivation in Drosophila larvae carrying a temperature-sensitive mutation in the shibire (shi1) gene was induced to mimic sedentary behavior during early life and [...] Read more.
The biological mechanisms linking sedentary lifestyles and metabolic derangements are incompletely understood. In this study, temporal muscle inactivation in Drosophila larvae carrying a temperature-sensitive mutation in the shibire (shi1) gene was induced to mimic sedentary behavior during early life and study its transcriptional outcome. Our findings indicated a significant change in the epigenetic profile, as well as the genomic profile, of RNA Pol II binding in the inactive muscles relative to control, within a relatively short time period. Whole-genome analysis of RNA-Pol II binding to DNA by muscle-specific targeted DamID (TaDa) protocol revealed that muscle inactivity altered Pol II binding in 121 out of 2010 genes (6%), with a three-fold enrichment of genes coding for lncRNAs. The suppressed protein-coding genes included genes associated with longevity, DNA repair, muscle function, and ubiquitin-dependent proteostasis. Moreover, inducing muscle inactivation exerted a multi-level impact upon chromatin modifications, triggering an altered epigenetic balance of active versus inactive marks. The downregulated genes in the inactive muscles included genes essential for muscle structure and function, carbohydrate metabolism, longevity, and others. Given the multiple analogous genes in Drosophila for many human genes, extrapolating our findings to humans may hold promise for establishing a molecular link between sedentary behavior and metabolic diseases. Full article
(This article belongs to the Topic Molecular Mechanisms of Exercise and Healthspan)
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7 pages, 227 KiB  
Commentary
Physical Exercise and Appetite Regulation: New Insights
by Lorenzo Caruso, Enrico Zauli and Mauro Vaccarezza
Biomolecules 2023, 13(8), 1170; https://doi.org/10.3390/biom13081170 - 27 Jul 2023
Cited by 2 | Viewed by 2284
Abstract
Physical exercise is considered an important physiological intervention able to prevent cardiovascular diseases, obesity, and obesity-related cardiometabolic imbalance. Nevertheless, basic molecular mechanisms that govern the metabolic benefits of physical exercise are poorly understood. Recent data unveil new mechanisms that potentially explain the link [...] Read more.
Physical exercise is considered an important physiological intervention able to prevent cardiovascular diseases, obesity, and obesity-related cardiometabolic imbalance. Nevertheless, basic molecular mechanisms that govern the metabolic benefits of physical exercise are poorly understood. Recent data unveil new mechanisms that potentially explain the link between exercise, feeding suppression, and obesity. Full article
(This article belongs to the Topic Molecular Mechanisms of Exercise and Healthspan)
14 pages, 2372 KiB  
Article
Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway
by Xiaomao Luo, Huiling Zhang, Xiaorui Cao, Ding Yang, Yi Yan, Jiayin Lu, Xiaonan Wang and Haidong Wang
Int. J. Mol. Sci. 2023, 24(14), 11401; https://doi.org/10.3390/ijms241411401 - 13 Jul 2023
Cited by 5 | Viewed by 1941
Abstract
Fgf21 has been identified as playing a regulatory role in muscle growth and function. Although the mechanisms through which endurance training regulates skeletal muscle have been widely studied, the contribution of Fgf21 remains poorly understood. Here, muscle size and function were measured, and [...] Read more.
Fgf21 has been identified as playing a regulatory role in muscle growth and function. Although the mechanisms through which endurance training regulates skeletal muscle have been widely studied, the contribution of Fgf21 remains poorly understood. Here, muscle size and function were measured, and markers of fiber type were evaluated using immunohistochemistry, immunoblots, or qPCR in endurance-exercise-trained wild-type and Fgf21 KO mice. We also investigated Fgf21-induced fiber conversion in C2C12 cells, which were incubated with lentivirus and/or pathway inhibitors. We found that endurance exercise training enhanced the Fgf21 levels of liver and GAS muscle and exercise capacity and decreased the distribution of skeletal muscle fiber size, and fast-twitch fibers were observed converting to slow-twitch fibers in the GAS muscle of mice. Fgf21 promoted the markers of fiber-type transition and eMyHC-positive myotubes by inhibiting the TGF-β1 signaling axis and activating the p38 MAPK signaling pathway without apparent crosstalk. Our findings suggest that the transformation and function of skeletal muscle fiber types in response to endurance training could be mediated by Fgf21 and its downstream signaling pathways. Our results illuminate the mechanisms of Fgf21 in endurance-exercise-induced fiber-type conversion and suggest a potential use of Fgf21 in improving muscle health and combating fatigue. Full article
(This article belongs to the Topic Molecular Mechanisms of Exercise and Healthspan)
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20 pages, 3047 KiB  
Article
Skeletal Muscle MicroRNA Patterns in Response to a Single Bout of Exercise in Females: Biomarkers for Subsequent Training Adaptation?
by Alexandra Grieb, Angelika Schmitt, Annunziata Fragasso, Manuel Widmann, Felipe Mattioni Maturana, Christof Burgstahler, Gunnar Erz, Philipp Schellhorn, Andreas M. Nieß and Barbara Munz
Biomolecules 2023, 13(6), 884; https://doi.org/10.3390/biom13060884 - 24 May 2023
Cited by 1 | Viewed by 1603
Abstract
microRNAs (miRs) have been proposed as a promising new class of biomarkers in the context of training adaptation. Using microarray analysis, we studied skeletal muscle miR patterns in sedentary young healthy females (n = 6) before and after a single submaximal bout [...] Read more.
microRNAs (miRs) have been proposed as a promising new class of biomarkers in the context of training adaptation. Using microarray analysis, we studied skeletal muscle miR patterns in sedentary young healthy females (n = 6) before and after a single submaximal bout of endurance exercise (‘reference training’). Subsequently, participants were subjected to a structured training program, consisting of six weeks of moderate-intensity continuous endurance training (MICT) and six weeks of high-intensity interval training (HIIT) in randomized order. In vastus lateralis muscle, we found significant downregulation of myomiRs, specifically miR-1, 133a-3p, and -5p, -133b, and -499a-5p. Similarly, exercise-associated miRs-23a-3p, -378a-5p, -128-3p, -21-5p, -107, -27a-3p, -126-3p, and -152-3p were significantly downregulated, whereas miR-23a-5p was upregulated. Furthermore, in an untargeted approach for differential expression in response to acute exercise, we identified n = 35 miRs that were downregulated and n = 20 miRs that were upregulated by factor 4.5 or more. Remarkably, KEGG pathway analysis indicated central involvement of this set of miRs in fatty acid metabolism. To reproduce these data in a larger cohort of all-female subjects (n = 29), qPCR analysis was carried out on n = 15 miRs selected from the microarray, which confirmed their differential expression. Furthermore, the acute response, i.e., the difference between miR concentrations before and after the reference training, was correlated with changes in maximum oxygen uptake (V̇O2max) in response to the training program. Here, we found that miRs-199a-3p and -19b-3p might be suitable acute-response candidates that correlate with individual degrees of training adaptation in females. Full article
(This article belongs to the Topic Molecular Mechanisms of Exercise and Healthspan)
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18 pages, 1279 KiB  
Article
Exercise-Induced Alternations of Adiponectin, Interleukin-8 and Indicators of Carbohydrate Metabolism in Males with Metabolic Syndrome
by Karol Makiel, Agnieszka Suder, Aneta Targosz, Marcin Maciejczyk and Alon Haim
Biomolecules 2023, 13(5), 852; https://doi.org/10.3390/biom13050852 - 18 May 2023
Cited by 3 | Viewed by 2414
Abstract
Adiponectin (ADIPO) and interleukin-8 (IL-8) are proteins that play a significant, albeit opposing, role in metabolic syndrome (MetS). The reported data on the effect of physical activity on the levels of these hormones in the population of people with MetS are conflicting. The [...] Read more.
Adiponectin (ADIPO) and interleukin-8 (IL-8) are proteins that play a significant, albeit opposing, role in metabolic syndrome (MetS). The reported data on the effect of physical activity on the levels of these hormones in the population of people with MetS are conflicting. The aim of the study was to evaluate the changes in hormone concentrations, insulin-resistance indices and body composition after two types of training. The study included 62 men with MetS (age 36.6 ± 6.9 years, body fat [BF] = 37.53 ± 4.5%), randomly assigned to: an experimental group EG1 (n = 21) with aerobic exercise intervention, an experimental group EG2 (n = 21) with combined aerobic and resistance exercise intervention, both for 12 weeks, and a control group CG (n = 20) without interventions. Anthropometric measurements and body composition (fat-free mass [FFM], gynoid body fat [GYNOID]), as well as a biochemical blood analysis (adiponectin [ADIPO], interleukin-8 [IL-8], homeostatic model assessment—adiponectin (HOMA-AD) and homeostatic model assessment—triglycerides (HOMA-TG) were performed at baseline, and at 6 and 12 weeks of intervention and 4 weeks after the intervention (follow-up). Intergroup (between groups) and intragroup (within each group) changes were statistically evaluated. In the experimental groups EG1 and EG2, no significant changes were observed in the ADIPO concentration, but a decrease of GYNOID and insulin-resistance indices was confirmed. The aerobic training led to favorable changes in IL-8 concentration. The use of combined resistance and aerobic training led to improved body composition, decreased waist circumference and better insulin-resistance indices in men with MetS. Full article
(This article belongs to the Topic Molecular Mechanisms of Exercise and Healthspan)
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11 pages, 3978 KiB  
Article
Both Acute and Consecutive Days of Formoterol Stimulation Influence Myogenic, Mitochondrial, and myomiR Gene Expression in Human Skeletal Muscle Cells
by Ryan A. Gordon, Emily L. Zumbro, Gena D. Guerin, Matthew L. Sokoloski, Vic Ben-Ezra, Christopher S. Brower, Rhett B. Rigby and Anthony A. Duplanty
Muscles 2023, 2(1), 86-96; https://doi.org/10.3390/muscles2010008 - 22 Feb 2023
Viewed by 1778
Abstract
Skeletal muscle physiology is regulated by microRNA that are localized within skeletal muscle (myomiRs). This study investigated how the expression of myomiRs and genes regulating skeletal muscle mass and myogenesis are influenced in response to acute and consecutive days of exercise-related signaling using [...] Read more.
Skeletal muscle physiology is regulated by microRNA that are localized within skeletal muscle (myomiRs). This study investigated how the expression of myomiRs and genes regulating skeletal muscle mass and myogenesis are influenced in response to acute and consecutive days of exercise-related signaling using the exercise mimetic, formoterol, in vitro. Human skeletal muscle cells were proliferated and differentiated for 6 days. Experimental conditions included: (a) control, (b) acute formoterol stimulation (AFS), and (c) consecutive days of formoterol stimulation (CFS). For AFS, myotubes were treated with 30 nM of formoterol for three hours on day 6 of differentiation, and this was immediately followed by RNA extraction. For CFS, myotubes were treated with 30 nM of formoterol for three hours on two or three consecutive days, with RNA extracted immediately following the final three-hour formoterol treatment. We observed increased myomiR expression for both AFS and CFS. AFS appeared to promote myogenesis, but this effect was lost with CFS. Additionally, we observed increased expression of genes involved in metabolism, mitochondrial biogenesis, and muscle protein degradation in response to AFS. myomiR and gene expression appear to be sensitive to acute and long-term exercise-related stimuli, and this likely contributes to the regulation of skeletal muscle mass. Full article
(This article belongs to the Topic Molecular Mechanisms of Exercise and Healthspan)
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