Special Issue "Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 July 2019).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Italia Di Liegro
Website
Guest Editor
Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), Universita degli Studi di Palermo, Palermo, Italy
Interests: brain cells; blood-brain barrier; RNA-binding proteins; extracellular vesicles; histone variants

Special Issue Information

Dear Colleagues,

From an evolutionary perspective, our species has relied on physical activity for most of its history (and still does) to survive and has had to escape from predators, to scavenge for food, and to use its physique to work or build necessary means for everyday life. Physical activity has been part of our evolution and progress since the very beginning, and consequently, our entire body has been programmed to be active physically and not to have a sedentary life.

However, only recently have we started to experience the consequences of the profound modifications that technology, together with highly energetic food diets, have brought into our daily lives. Thus, a lot of initiatives aim to reverse this situation and promote physical activity as a keystone for our health and happiness.

In the last twenty years, it has become increasingly clear from scientific research that our ancient survival principle has beneficial effects not only on the cells and organs involved in physical activities but on the metabolism of the entire organism, influencing the homeostasis and integration of all bodily functions, likely stimulating the production of hormones and other regulatory molecules, with each affecting vital signalling pathways.

On the contrary, the cellular and molecular mechanisms underlying all these integrated effects still remain obscure. Single molecules, such as the brain derived neurotrophic factor (BDNF) or even lactate, have been referred to as causative factors and been examined at a molecular level in different cells. Most of the web of factors involved in the molecular signalling upon exercise is suspected to be centrally controlled by the brain, which has been indeed reported to be deeply modified by physical activity. Lately, the chromatin structure and epigenetic marks (and thus gene expression) have been reported to be modulated upon physical activity and help in the treatment of pathologies as different as Alzheimer’s disease, diabetes, and multiple sclerosis.

Such complexity requires a multifaceted approach to shed light on the molecular interactions that occur between physical activity and its outcome at a cellular level. For this reason, we decided to bring together a collection of research articles and reviews from which new ideas could be obtained and shared.

Prof. Italia Di Liegro
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • epigenetics
  • physical exercise
  • transgenerational inheritance
  • therapy
  • vertebrates
  • brain cells
  • healthy lifestyle
  • central control of metabolism

Published Papers (11 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

Open AccessEditorial
Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise
Genes 2019, 10(12), 1043; https://doi.org/10.3390/genes10121043 - 16 Dec 2019
Cited by 2
Abstract
Since ancient times, the importance of physical activity (PA) and of a wholesome diet for human health has been clearly recognized. However, only recently, it has been acknowledged that PA can reverse at least some of the unwanted effects of a sedentary lifestyle, [...] Read more.
Since ancient times, the importance of physical activity (PA) and of a wholesome diet for human health has been clearly recognized. However, only recently, it has been acknowledged that PA can reverse at least some of the unwanted effects of a sedentary lifestyle, contributing to the treatment of pathologies such as hypertension and diabetes, to the delay of aging and neurodegeneration, and even to the improvement of immunity and cognitive processes. At the same time, the cellular and molecular bases of these effects are beginning to be uncovered. The original research articles and reviews published in this Special Issue on “Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise” focus on different aspects of the genetics and molecular biology of PA effects on health and, in addition, on the effects of different genotypes on the ability to perform PA. All authors have read and agreed to the published version of the manuscript. Full article
Show Figures

Graphical abstract

Research

Jump to: Editorial, Review, Other

Open AccessArticle
Genetically Determined Physical Activity and Its Association with Circulating Blood Cells
Genes 2019, 10(11), 908; https://doi.org/10.3390/genes10110908 - 07 Nov 2019
Cited by 1
Abstract
Lower levels of physical activity (PA) have been associated with increased risk of cardiovascular disease. Worldwide, there is a shift towards a lifestyle with less PA, posing a serious threat to public health. One of the suggested mechanisms behind the association between PA [...] Read more.
Lower levels of physical activity (PA) have been associated with increased risk of cardiovascular disease. Worldwide, there is a shift towards a lifestyle with less PA, posing a serious threat to public health. One of the suggested mechanisms behind the association between PA and disease development is through systemic inflammation, in which circulating blood cells play a pivotal role. In this study we investigated the relationship between genetically determined PA and circulating blood cells. We used 68 single nucleotide polymorphisms associated with objectively measured PA levels to perform a Mendelian randomization analysis on circulating blood cells in 222,645 participants of the UK Biobank. For inverse variance fixed effects Mendelian randomization analyses, p < 1.85 × 10−3 (Bonferroni-adjusted p-value of 0.05/27 tests) was considered statistically significant. Genetically determined increased PA was associated with decreased lymphocytes (β = –0.03, SE = 0.008, p = 1.35 × 10−3) and decreased eosinophils (β = –0.008, SE = 0.002, p = 1.36 × 10−3). Although further mechanistic studies are warranted, these findings suggest increased physical activity is associated with an improved inflammatory state with fewer lymphocytes and eosinophils. Full article
Show Figures

Figure 1

Open AccessArticle
GCKR rs780094 Polymorphism as A Genetic Variant Involved in Physical Exercise
Genes 2019, 10(8), 570; https://doi.org/10.3390/genes10080570 - 28 Jul 2019
Cited by 2
Abstract
Exercise performance is influenced by genetics. However, there is a lack of knowledge about the role played by genetic variability in the frequency of physical exercise practice. The objective was to identify genetic variants that modulate the commitment of people to perform physical [...] Read more.
Exercise performance is influenced by genetics. However, there is a lack of knowledge about the role played by genetic variability in the frequency of physical exercise practice. The objective was to identify genetic variants that modulate the commitment of people to perform physical exercise and to detect those subjects with a lower frequency practice. A total of 451 subjects were genotyped for 64 genetic variants related to inflammation, circadian rhythms, vascular function as well as energy, lipid and carbohydrate metabolism. Physical exercise frequency question and a Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ) were used to qualitatively and quantitatively measure the average amount of physical exercise. Dietary intake and energy expenditure due to physical activity were also studied. Differences between genotypes were analyzed using linear and logistic models adjusted for Bonferroni. A significant association between GCKR rs780094 and the times the individuals performed physical exercise was observed (p = 0.004). The carriers of the minor allele showed a greater frequency of physical exercise in comparison to the major homozygous genotype carriers (OR: 1.86, 95% CI: 1.36–2.56). The analysis of the GCKR rs780094 variant suggests a possible association with the subjects that present lower frequency of physical exercise. Nevertheless, future studies are needed to confirm these findings. Full article
Show Figures

Figure 1

Open AccessArticle
Changes in Serum Iron and Leukocyte mRNA Levels of Genes Involved in Iron Metabolism in Amateur Marathon Runners—Effect of the Running Pace
Genes 2019, 10(6), 460; https://doi.org/10.3390/genes10060460 - 15 Jun 2019
Cited by 2
Abstract
Iron is essential for physical activity due to its role in energy production pathways and oxygen transportation via hemoglobin and myoglobin. Changes in iron-related biochemical parameters after physical exercise in athletes are of substantial research interest, but molecular mechanisms such as gene expression [...] Read more.
Iron is essential for physical activity due to its role in energy production pathways and oxygen transportation via hemoglobin and myoglobin. Changes in iron-related biochemical parameters after physical exercise in athletes are of substantial research interest, but molecular mechanisms such as gene expression are still rarely tested in sports. In this paper, we evaluated the mRNA levels of genes related to iron metabolism (PCBP1, PCBP2, FTL, FTH, and TFRC) in leukocytes of 24 amateur runners at four time points: before, immediately after, 3 h after, and 24 h after a marathon. We measured blood morphology as well as serum concentrations of iron, ferritin, and C-reactive protein (CRP). Our results showed significant changes in gene expression (except for TFRC), serum iron, CRP, and morphology after the marathon. However, the alterations in mRNA and protein levels occurred at different time points (immediately and 3 h post-run, respectively). The levels of circulating ferritin remained stable, whereas the number of transcripts in leukocytes differed significantly. We also showed that running pace might influence mRNA expression. Our results indicated that changes in the mRNA of genes involved in iron metabolism occurred independently of serum iron and ferritin concentrations. Full article
Show Figures

Figure 1

Open AccessArticle
Association between Aerobic Exercise and High-Density Lipoprotein Cholesterol Levels across Various Ranges of Body Mass Index and Waist-Hip Ratio and the Modulating Role of the Hepatic Lipase rs1800588 Variant
Genes 2019, 10(6), 440; https://doi.org/10.3390/genes10060440 - 10 Jun 2019
Cited by 1
Abstract
Changes in concentrations of high-density lipoprotein cholesterol (HDL-C) are modified by several factors. We examined the relationship between aerobic exercise and HDL-C among different categories of body mass index (BMI) and waist-hip ratio (WHR) and the impact of rs1800588 variant in the hepatic [...] Read more.
Changes in concentrations of high-density lipoprotein cholesterol (HDL-C) are modified by several factors. We examined the relationship between aerobic exercise and HDL-C among different categories of body mass index (BMI) and waist-hip ratio (WHR) and the impact of rs1800588 variant in the hepatic lipase (LIPC) gene. We analyzed data from 6184 men and 8353 women aged 30–70 years. Participants were grouped into two WHR categories: Normal (0 < WHR < 0.9 for men and 0 < WHR < 0.8 for women) and abnormal (WHR ≥ 0.9 for men and WHR ≥ 0.8 for women). The BMI categories were: Underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24 kg/m2), overweight (24 ≤ BMI < 27 kg/m2), and obese (BMI ≥ 27 kg/m2). Multivariate linear regression models were used to investigate associations between HDL-C and exercise. Aerobic exercise was significantly associated with higher HDL-C (β = 1.18325; p < 0.0001) when compared with no exercise. HDL-C was significantly lower in persons with abnormal compared to those with normal WHR (β = −3.06689; p < 0.0001). Compared with normal weight, overweight and obese categories were associated with lower HDL-C, with β values of −4.31095 and −6.44230, respectively (p < 0.0001). Unlike rs1800588 CT and TT genotypes, associations between aerobic exercise and HDL were not significant among CC carriers no matter their BMI or WHR. Full article
Open AccessArticle
ACTN3 R577X Genotype and Exercise Phenotypes in Recreational Marathon Runners
Genes 2019, 10(6), 413; https://doi.org/10.3390/genes10060413 - 29 May 2019
Cited by 6
Abstract
Background: Homozygosity for the X-allele in the ACTN3 R577X (rs1815739) polymorphism results in the complete absence of α-actinin-3 in sarcomeres of fast-type muscle fibers. In elite athletes, the ACTN3 XX genotype has been related to inferior performance in speed and power-oriented sports; [...] Read more.
Background: Homozygosity for the X-allele in the ACTN3 R577X (rs1815739) polymorphism results in the complete absence of α-actinin-3 in sarcomeres of fast-type muscle fibers. In elite athletes, the ACTN3 XX genotype has been related to inferior performance in speed and power-oriented sports; however, its influence on exercise phenotypes in recreational athletes has received less attention. We sought to determine the influence of ACTN3 genotypes on common exercise phenotypes in recreational marathon runners. Methods: A total of 136 marathoners (116 men and 20 women) were subjected to laboratory testing that included measurements of body composition, isometric muscle force, muscle flexibility, ankle dorsiflexion, and the energy cost of running. ACTN3 genotyping was performed using TaqMan probes. Results: 37 runners (27.2%) had the RR genotype, 67 (49.3%) were RX and 32 (23.5%) were XX. There was a difference in body fat percentage between RR and XX genotype groups (15.7 ± 5.8 vs. 18.8 ± 5.5%; effect size, ES, = 0.5 ± 0.4, p = 0.024), whereas the distance obtained in the sit-and-reach-test was likely lower in the RX than in the XX group (15.3 ± 7.8 vs. 18.4 ± 9.9 cm; ES = 0.4 ± 0.4, p = 0.046). Maximal dorsiflexion during the weight-bearing lunge test was different in the RR and XX groups (54.8 ± 5.8 vs. 57.7 ± 5.1 degree; ES = 0.5 ± 0.5, p = 0.044). Maximal isometric force was higher in the RR than in the XX group (16.7 ± 4.7 vs. 14.7 ± 4.0 N/kg; ES = −0.5 ± 0.3, p = 0.038). There was no difference in the energy cost of running between genotypes (~4.8 J/kg/min for all three groups, ES ~0.2 ± 0.4). Conclusions: The ACTN3 genotype might influence several exercise phenotypes in recreational marathoners. Deficiency in α-actinin-3 might be accompanied by higher body fatness, lower muscle strength and higher muscle flexibility and range of motion. Although there is not yet a scientific rationale for the use of commercial genetic tests to predict sports performance, recreational marathon runners who have performed such types of testing and have the ACTN3 XX genotype might perhaps benefit from personalized strength training to improve their performance more than their counterparts with other ACTN3 genotypes. Full article
Show Figures

Figure 1

Review

Jump to: Editorial, Research, Other

Open AccessReview
Physical Activity and Brain Health
Genes 2019, 10(9), 720; https://doi.org/10.3390/genes10090720 - 17 Sep 2019
Cited by 8
Abstract
Physical activity (PA) has been central in the life of our species for most of its history, and thus shaped our physiology during evolution. However, only recently the health consequences of a sedentary lifestyle, and of highly energetic diets, are becoming clear. It [...] Read more.
Physical activity (PA) has been central in the life of our species for most of its history, and thus shaped our physiology during evolution. However, only recently the health consequences of a sedentary lifestyle, and of highly energetic diets, are becoming clear. It has been also acknowledged that lifestyle and diet can induce epigenetic modifications which modify chromatin structure and gene expression, thus causing even heritable metabolic outcomes. Many studies have shown that PA can reverse at least some of the unwanted effects of sedentary lifestyle, and can also contribute in delaying brain aging and degenerative pathologies such as Alzheimer’s Disease, diabetes, and multiple sclerosis. Most importantly, PA improves cognitive processes and memory, has analgesic and antidepressant effects, and even induces a sense of wellbeing, giving strength to the ancient principle of “mens sana in corpore sano” (i.e., a sound mind in a sound body). In this review we will discuss the potential mechanisms underlying the effects of PA on brain health, focusing on hormones, neurotrophins, and neurotransmitters, the release of which is modulated by PA, as well as on the intra- and extra-cellular pathways that regulate the expression of some of the genes involved. Full article
Show Figures

Graphical abstract

Open AccessReview
Ketogenic Diet and Microbiota: Friends or Enemies?
Genes 2019, 10(7), 534; https://doi.org/10.3390/genes10070534 - 15 Jul 2019
Cited by 10
Abstract
Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence [...] Read more.
Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence of such a microbial community on human health and its multiple mechanisms of action as the production of bioactive compounds, pathogens protection, energy homeostasis, nutrients metabolism and regulation of immunity, establishing the influences of different nutritional approach is of pivotal importance. The very low carbohydrate ketogenic diet is a very popular dietary approach used for different aims: from weight loss to neurological diseases. The aim of this review is to dissect the complex interactions between ketogenic diet and gut microbiota and how this large network may influence human health. Full article
Show Figures

Figure 1

Open AccessReview
Physical Activity Might Reduce the Adverse Impacts of the FTO Gene Variant rs3751812 on the Body Mass Index of Adults in Taiwan
Genes 2019, 10(5), 354; https://doi.org/10.3390/genes10050354 - 09 May 2019
Cited by 2
Abstract
The fat mass and obesity-associated (FTO) gene is a significant genetic contributor to polygenic obesity. We investigated whether physical activity (PA) modulates the effect of FTO rs3751812 on body mass index (BMI) among Taiwanese adults. Analytic samples included 10,853 Taiwan biobank [...] Read more.
The fat mass and obesity-associated (FTO) gene is a significant genetic contributor to polygenic obesity. We investigated whether physical activity (PA) modulates the effect of FTO rs3751812 on body mass index (BMI) among Taiwanese adults. Analytic samples included 10,853 Taiwan biobank participants. Association of the single-nucleotide polymorphism (SNP) with BMI was assessed using linear regression models. Physical activity was defined as any kind of exercise lasting 30 min each session, at least three times a week. Participants with heterozygous (TG) and homozygous (TT) genotypes had higher BMI compared to those with wild-type (GG) genotypes. The β value was 0.381(p < 0.0001) for TG individuals and 0.684 (p = 0.0204) for TT individuals. There was a significant dose-response effect among carriers of different risk alleles (p trend <0.0001). Active individuals had lower BMI than their inactive counterparts (β = −0.389, p < 0.0001). Among the active individuals, significant associations were found only with the TG genotype (β = 0.360, p = 0.0032). Inactive individuals with TG and TT genotypes had increased levels of BMI compared to those with GG genotypes: Their β values were 0.381 (p = 0.0021) and 0.950 (p = 0.0188), respectively. There was an interaction between the three genotypes, physical inactivity, and BMI (p trend  = 0.0002). Our data indicated that increased BMI owing to genetic susceptibility by FTO rs3751812 may be reduced by physical activity. Full article
Open AccessReview
A Systematically Assembled Signature of Genes to be Deep-Sequenced for Their Associations with the Blood Pressure Response to Exercise
Genes 2019, 10(4), 295; https://doi.org/10.3390/genes10040295 - 11 Apr 2019
Cited by 2
Abstract
Background: Exercise is one of the best nonpharmacologic therapies to treat hypertension. The blood pressure (BP) response to exercise is heritable. Yet, the genetic basis for the antihypertensive effects of exercise remains elusive. Methods: To assemble a prioritized gene signature, we performed [...] Read more.
Background: Exercise is one of the best nonpharmacologic therapies to treat hypertension. The blood pressure (BP) response to exercise is heritable. Yet, the genetic basis for the antihypertensive effects of exercise remains elusive. Methods: To assemble a prioritized gene signature, we performed a systematic review with a series of Boolean searches in PubMed (including Medline) from earliest coverage. The inclusion criteria were human genes in major BP regulatory pathways reported to be associated with: (1) the BP response to exercise; (2) hypertension in genome-wide association studies (GWAS); (3) the BP response to pharmacotherapy; (4a) physical activity and/or obesity in GWAS; and (4b) BP, physical activity, and/or obesity in non-GWAS. Included GWAS reports disclosed the statistically significant thresholds used for multiple testing. Results: The search yielded 1422 reports. Of these, 57 trials qualified from which we extracted 11 genes under criteria 1, 18 genes under criteria 2, 28 genes under criteria 3, 27 genes under criteria 4a, and 29 genes under criteria 4b. We also included 41 genes identified from our previous work. Conclusions: Deep-sequencing the exons of this systematically assembled signature of genes represents a cost and time efficient approach to investigate the genomic basis for the antihypertensive effects of exercise. Full article
Show Figures

Graphical abstract

Other

Open AccessConcept Paper
Impact of Acute Aerobic Exercise on Genome-Wide DNA-Methylation in Natural Killer Cells—A Pilot Study
Genes 2019, 10(5), 380; https://doi.org/10.3390/genes10050380 - 19 May 2019
Cited by 5
Abstract
Natural Killer (NK-) cells reveal a keen reaction to acute bouts of exercise, including changes of epigenetic modifications. So far, exercise-induced alterations in NK-cell DNA-methylation were shown for single genes only. Studies analyzing genome-wide DNA-methylation have used conglomerates like peripheral blood mononuclear cells [...] Read more.
Natural Killer (NK-) cells reveal a keen reaction to acute bouts of exercise, including changes of epigenetic modifications. So far, exercise-induced alterations in NK-cell DNA-methylation were shown for single genes only. Studies analyzing genome-wide DNA-methylation have used conglomerates like peripheral blood mononuclear cells (PBMCs) rather than specific subsets of immune cells. Therefore, the aim of this pilot-study was to generate first insights into the influence of a single bout of exercise on genome-wide DNA-methylation in isolated NK-cells to open the field for such analyses. Five healthy women performed an incremental step test and blood samples were taken before and after exercise. DNA was isolated from magnet bead sorted NK-cells and further analyzed for global DNA-methylation using the Infinium MethylationEPIC BeadChip. DNA-methylation was changed at 33 targets after acute exercise. These targets were annotated to 25 genes. Of the targets, 19 showed decreased and 14 increased methylation. The 25 genes with altered DNA-methylation have different roles in cell regulation and differ in their molecular functions. These data give new insights in the exercise induced regulation of NK-cells. By using isolated NK-cells, exercise induced differences in DNA-methylation could be shown. Whether or not these changes lead to functional adaptions needs to be elucidated. Full article
Back to TopTop