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Exercise and Health: Cellular and Molecular Perspectives
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Exercise and Health: Cellular and Molecular Perspectives

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 11635

Special Issue Editor

Dr. Annamaria Mancini

E-Mail Website
Guest Editor
Department of Medical, Human Movement and Wellbeing Sciences, University of Naples Parthenope, 80133 Naples, Italy
Interests: exercise performance; nutrition in sport; c-miRNAs; DNA repair pathways; senescence suppression; protein quality control; exercise-induced autophagy; aging; microbiota

Special Issue Information

Dear Colleagues,

Exercise plays a pivotal role in promoting health, and understanding its impact requires exploring cellular and molecular perspectives. At the cellular level, regular exercise induces adaptations, such as increased mitochondrial density, enhancement of the cell’s ability to generate energy and improved overall cellular function. Molecular changes associated with exercise involve the activation of various signaling pathways, including AMP-activated protein kinase (AMPK) and mTOR, influencing protein synthesis, cellular metabolism, and growth. Exercise has been shown to modulate gene expression, promoting the production of proteins involved in antioxidant defense, inflammation regulation, and cellular repair. Aerobic exercise, such as running or cycling, triggers the release of neurotrophic factors like brain-derived neurotrophic factor (BDNF), fostering brain health and cognitive function at the molecular level. Resistance training induces molecular changes in muscle and bone tissue, stimulating the synthesis of contractile proteins and enhancing muscle strength and endurance. Cellular responses to exercise include improved insulin sensitivity, which is crucial in preventing and managing metabolic disorders like type 2 diabetes. Chronic inflammation, a contributor to various health issues, is mitigated by regular exercise through molecular mechanisms that regulate pro-inflammatory cytokines and anti-inflammatory mediators. Telomere length, a molecular marker of cellular aging, appears to be positively influenced by exercise, potentially slowing down the aging process at the cellular level. Understanding the intricate interplay between exercise, cellular adaptations, and molecular signaling provides valuable insights for developing targeted interventions to optimize health and prevent a range of chronic diseases.

Prof. Dr. Annamaria Mancini
Guest Editor

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Keywords

  • promoting health
  • anti-inflammatory action
  • anti-ageing action
  • mental health
  • mitochondrial adaptation
  • cellular function
  • regulation of gene expression
  • metabolic response to exercise

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Published Papers (4 papers)

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Research

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19 pages, 11922 KiB  
Article
The Potential Related Genes and Mechanisms Involved in Improving the Treadmill Exercise Ability of APP/PS1 Mice
by Zhe Zhao, Xingqing Wu, Weijia Wu, Yingzhe Tang, Xiangyuan Meng, Mei Peng, Changfa Tang, Lan Zheng and Wenfeng Liu
Int. J. Mol. Sci. 2024, 25(19), 10244; https://doi.org/10.3390/ijms251910244 - 24 Sep 2024
Viewed by 1441
Abstract
Alzheimer’s disease (AD) causes a decline in skeletal muscle function, which can further exacerbate the cognitive dysfunction of patients with AD. It has been widely established that exercise improves AD brain pathology, but the role of skeletal muscle in AD is still poorly [...] Read more.
Alzheimer’s disease (AD) causes a decline in skeletal muscle function, which can further exacerbate the cognitive dysfunction of patients with AD. It has been widely established that exercise improves AD brain pathology, but the role of skeletal muscle in AD is still poorly understood. In this study, we investigated the effects of treadmill exercise on the exercise ability of APP/PS1 transgenic AD mice and explored potential gene expression changes in their skeletal muscle. The APP/PS1 mice were subjected to a treadmill exercise for 12 weeks, followed by the Morris water maze and the open field test. After behavioral experiments, the changes in morphology, area, collagen fiber deposition, and ultrastructure of the skeletal muscle were determined; the balance of skeletal muscle protein synthesis and decomposition was analyzed; and changes in gene expression were investigated using RNA-Seq. We found that this exercise strategy can promote the learning and memory abilities of AD mice, reduce their anxiety-like behavior, improve their exercise ability, alleviate skeletal muscle atrophy, and optimize the microstructure. It can also enhance skeletal muscle protein synthesis and decomposition and improve several signaling pathways, such as the JAK–STAT, Wnt, and NOD-like receptors while decreasing calcium, cAMP, cGMP–PKG, and other signaling pathways. Six KEGG enrichment signaling pathways were downregulated and five signaling pathways were upregulated in the AD mice compared with wild-type mice, and these pathways were precisely reversed after the treadmill exercise. The expression of transcription factors such as Fosb and Egr1 in the skeletal muscle of AD mice decreased, followed by a decrease in the regulated target genes Socs1, Srrm4, and Il1b, a trend that was reversed following the exercise intervention. After exercise, AD mice exhibited a similar gene expression to that of wild-type mice, indicating enhanced exercise ability. The potential regulatory pathways and related genes identified in this study provide valuable insights for the clinical management and treatment of AD. Full article
(This article belongs to the Special Issue Exercise and Health: Cellular and Molecular Perspectives)
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15 pages, 1783 KiB  
Article
Concussion-Related Biomarker Variations in Retired Rugby Players and Implications for Neurodegenerative Disease Risk: The UK Rugby Health Study
by Norah Alanazi, Melinda Fitzgerald, Patria Hume, Sarah Hellewell, Alex Horncastle, Chidozie Anyaegbu, Melissa G. Papini, Natasha Hargreaves, Michal Halicki, Ian Entwistle, Karen Hind and Paul Chazot
Int. J. Mol. Sci. 2024, 25(14), 7811; https://doi.org/10.3390/ijms25147811 - 17 Jul 2024
Cited by 2 | Viewed by 4741
Abstract
The health and well-being of retired rugby union and league players, particularly regarding the long-term effects of concussions, are of major concern. Concussion has been identified as a major risk factor for neurodegenerative diseases, such as Alzheimer’s and Amyotrophic Lateral Sclerosis (ALS), in [...] Read more.
The health and well-being of retired rugby union and league players, particularly regarding the long-term effects of concussions, are of major concern. Concussion has been identified as a major risk factor for neurodegenerative diseases, such as Alzheimer’s and Amyotrophic Lateral Sclerosis (ALS), in athletes engaged in contact sports. This study aimed to assess differences in specific biomarkers between UK-based retired rugby players with a history of concussion and a non-contact sports group, focusing on biomarkers associated with Alzheimer’s, ALS, and CTE. We randomly selected a sample of male retired rugby or non-contact sport athletes (n = 56). The mean age was 41.84 ± 6.44, and the mean years since retirement from the sport was 7.76 ± 6.69 for participants with a history of substantial concussions (>5 concussions in their career) (n = 30). The mean age was 45.75 ± 11.52, and the mean years since retirement was 6.75 ± 4.64 for the healthy controls (n = 26). Serum biomarkers (t-tau, RBP-4, SAA, Nf-L, and retinol), plasma cytokines, and biomarkers associated with serum-derived exosomes (Aβ42, p-tau181, p-tau217, and p-tau231) were analyzed using validated commercial ELISA assays. The results of the selected biomarkers were compared between the two groups. Biomarkers including t-tau and p-tau181 were significantly elevated in the history of the substantial concussion group compared to the non-contact sports group (t-tau: p < 0.01; p-tau181: p < 0.05). Although between-group differences in p-tau217, p-tau231, SAA, Nf-L, retinol, and Aβ42 were not significantly different, there was a trend for higher levels of Aβ42, p-tau217, and p-tau231 in the concussed group. Interestingly, the serum-derived exosome sizes were significantly larger (p < 0.01), and serum RBP-4 levels were significantly reduced (p < 0.05) in the highly concussed group. These findings indicate that retired athletes with a history of multiple concussions during their careers have altered serum measurements of exosome size, t-tau, p-tau181, and RBP-4. These biomarkers should be explored further for the prediction of future neurodegenerative outcomes, including ALS, in those with a history of concussion. Full article
(This article belongs to the Special Issue Exercise and Health: Cellular and Molecular Perspectives)
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Review

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16 pages, 3249 KiB  
Review
The Complement System as a Part of Immunometabolic Post-Exercise Response in Adipose and Muscle Tissue
by Bartosz Wojciuk, Ignacy Frulenko, Andrzej Brodkiewicz, Dagmara Kita, Monica Baluta, Filip Jędrzejczyk, Marta Budkowska, Karolina Turkiewicz, Patrizia Proia, Andrzej Ciechanowicz, Dorota Kostrzewa-Nowak and Robert Nowak
Int. J. Mol. Sci. 2024, 25(21), 11608; https://doi.org/10.3390/ijms252111608 - 29 Oct 2024
Cited by 2 | Viewed by 1341
Abstract
The precise molecular processes underlying the complement’s activation, which follows exposure to physical stress still remain to be fully elucidated. However, some possible mechanisms could play a role in initiating changes in the complement’s activity, which are observed post-exposure to physical stress stimuli. [...] Read more.
The precise molecular processes underlying the complement’s activation, which follows exposure to physical stress still remain to be fully elucidated. However, some possible mechanisms could play a role in initiating changes in the complement’s activity, which are observed post-exposure to physical stress stimuli. These are mainly based on metabolic shifts that occur in the microenvironment of muscle tissue while performing its function with increased intensity, as well as the adipose tissue’s role in sterile inflammation and adipokine secretion. This review aims to discuss the current opinions on the possible link between the complement activation and diet, age, sex, and health disorders with a particular emphasis on endocrinopathies and, furthermore, the type of physical activity and overall physical fitness. It has been indicated that regular physical activity incorporated into therapeutic strategies potentially improves the management of particular diseases, such as, e.g., autoimmune conditions. Moreover, it represents a favorable influence on immunoaging processes. A better understanding of the complement system’s interaction with physical activity will support established clinical therapies targeting complement components. Full article
(This article belongs to the Special Issue Exercise and Health: Cellular and Molecular Perspectives)
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17 pages, 572 KiB  
Review
The Effect of Physical Activity/Exercise on miRNA Expression and Function in Non-Communicable Diseases—A Systematic Review
by Moomna Afzal, Francesca Greco, Federico Quinzi, Francesca Scionti, Samantha Maurotti, Tiziana Montalcini, Annamaria Mancini, Pasqualina Buono and Gian Pietro Emerenziani
Int. J. Mol. Sci. 2024, 25(13), 6813; https://doi.org/10.3390/ijms25136813 - 21 Jun 2024
Cited by 3 | Viewed by 3176
Abstract
Exercise may differently affect the expression of key molecular markers, including skeletal muscle and circulating miRNAs, involved in cellular and metabolic pathways’ regulation in healthy individuals and in patients suffering from non-communicable diseases (NCDs). Epigenetic factors are emerging as potential therapeutic biomarkers in [...] Read more.
Exercise may differently affect the expression of key molecular markers, including skeletal muscle and circulating miRNAs, involved in cellular and metabolic pathways’ regulation in healthy individuals and in patients suffering from non-communicable diseases (NCDs). Epigenetic factors are emerging as potential therapeutic biomarkers in the prognosis and treatment of NCDs and important epigenetic factors, miRNAs, play a crucial role in cellular pathways. This systematic review aims to underline the potential link between changes in miRNA expression after different types of physical activity/exercise in some populations affected by NCDs. In June 2023, we systematically investigated the following databases: PubMed, MEDLINE, Scopus, and Web of Science, on the basis of our previously established research questions and following the PRISMA guidelines. The risk of bias and quality assessment were, respectively, covered by ROB2 and the Newcastle Ottawa scale. Of the 1047 records extracted from the initial search, only 29 studies were found to be eligible. In these studies, the authors discuss the association between exercise-modulated miRNAs and NCDs. The NCDs included in the review are cancer, cardiovascular diseases (CVDs), chronic obstructive pulmonary disease (COPD), and type 2 diabetes mellitus (T2DM). We evidenced that miR-146, miR-181, miR-133, miR-21, and miRNA-1 are the most reported miRNAs that are modulated by exercise. Their expression is associated with an improvement in health markers and they may be a potential target in terms of the development of future therapeutic tools. Full article
(This article belongs to the Special Issue Exercise and Health: Cellular and Molecular Perspectives)
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