Transcriptional and Epigenetic Response to Sedentary Behavior and Physical Activity in Children and Adolescents: A Systematic Review

Abstract

Background: The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are poorly understood. We aimed to synthesize the current knowledge of the association of sedentary behavior and physical activity (acute and chronic effects) with gene expression and epigenetic modifications in children and adolescents.

Methods: PubMed, Web of Science, and Scopus databases were systematically searched until April 2022. A total of 15 articles were eligible for this review. The risk of bias assessment was performed using the Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews and/or a modified version of the Downs and Black checklist.

Results: Thirteen studies used candidate gene approach, while only 2 studies performed high-throughput analyses. The candidate genes significantly linked to sedentary behavior or physical activity were: FOXP3, HSD11B2, IL-10, TNF-α, ADRB2, VEGF, HSP70, SOX, and GPX. Non-coding Ribonucleic acids (RNAs) regulated by sedentary behavior or physical activity were: miRNA-222, miRNA-146^a, miRNA-16, miRNA-126, miR-320^a, and long non-coding RNA MALAT1. These molecules are involved in inflammation, immune function, angiogenic process, and cardiovascular disease. Transcriptomics analyses detected thousands of genes that were altered following an acute bout of physical activity and are linked to gene pathways related to immune function, apoptosis, and metabolic diseases.

Conclusion: The evidence found to date is rather limited. Multidisciplinary studies are essential to characterize the molecular mechanisms in response to sedentary behavior and physical activity in the pediatric population. Larger cohorts and randomized controlled trials, in combination with multi-omics analyses, may provide the necessary data to bring the field forward.

Systematic review registration: [www.ClinicalTrials.gov], identifier [CRD42021235431].

Keywords: RNA-seq; epigenomics; exercise; methylation; omics; physical fitness.

FIGURE 1

Study selection process based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flow diagram.

FIGURE 2

Summary of the main candidate genes and gene pathways related to sedentary behavior (SB) and physical activity (PA) (i.e., acute and chronic effects) in the pediatric population. (A) Exposure: SB and PA (acute and chronic effects). (B) Outcomes: gene expression and epigenetics (candidate genes and high-throughput transcriptomics analyses). (C) Main findings: relevant genes identified in our systematic review. Green arrows reflect up-regulation and red arrows down-regulation. This figure was created with BioRender.com.

FIGURE 3

The complex integration of “omics” data (i.e., multi-omics analysis) might contribute to a better understanding of the molecular mechanisms underlying the health-related benefits of physical activity in children and adolescents. The human genome is essentially invariant and comprises more than 25,000 genes, which encode ∼100,000–200,000 transcripts and 1 million proteins, and a smaller number of metabolites (2,500–3,000) make up the human metabolome (71). The epigenome, which can be influenced by physical activity in adults (15), shows a low/moderate temporal variance and influences both transcriptome and proteome. The transcriptome can be affected by a single bout of physical activity (36, 37) in children and presents a high temporal variance and is translated into the proteome, influencing the metabolome in a tissue-specific manner. Figure modified from Altmäe et al. (72) with permission of the Publisher. This figure was created with BioRender.com.