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Physical Activity as a Preventive Lifestyle Intervention Acts Through Specific Exosomal miRNA Species-Evidence From Human Short- and Long-Term Pilot Studies.

ABSTRACT: Exercise initiates systemic adaptation to promote health and prevent various lifestyle-related chronic diseases. Emerging evidence suggests that circulating exosomes mediate some of the beneficial effects of exercise via the transfer of microRNAs between tissues. Yet to date, a comprehensive profile of the exosomal miRNA (exomiR) content released following short-term (0.5 year in this study) and long-term (25 + years in this study) regular bouts of exercise is still lacking. However, a better understanding of these miRNA species would assist in clarifying the role of regular exercise at the molecular level in the prevention of chronic diseases. In the present pilot studies we analyzed serum exomiR expression in healthy young, sedentary participants (n = 14; age: 23 ± 2 years) at baseline and following a half year-long moderate-intensity regular exercise training. We also analyzed serum exomiR expression in older, healthy trained participants (seniors, n = 11; age: 62 ± 6 years) who engaged in endurance activities for at least 25 years. Following the isolation and enrichment of serum exosomes using Total Exosome Isolation Reagent (TEI) their exomiR levels were determined using the amplification-free Nanostring platform. Hierarchical cluster analysis revealed that the majority of exomiRs overlap for short-term (0.5 year in this study) and long-term (25 + years in this study) regular bouts of exercise. The top 12 significantly altered exomiRs (let-7a-5p; let-7g-5p; miR-130a-3p; miR-142-3p; miR-150-5p; miR-15a-5p; miR-15b-5p; miR-199a-3p; miR-199b-3p; miR-223-3p; miR-23a-3p, and miR-451a-3p) were used for further evaluation. According to KEGG pathway analysis a large portion of the exomiRs target chronic diseases including cancer, neurodegenerative and metabolic diseases, and viral infections. Our results provide evidence that exosomal miRNA modulation is the molecular mechanism through which regular exercise prevents various chronic diseases. The possibility of using such exomiRs to target diseases is of great interest. While further validation is needed, our comprehensive exomiR study presents, for the first time, the disease-preventive molecular pattern of both short and long-term regular exercise.

SUBMITTER: Garai K

PROVIDER: S-EPMC8365358 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPeople with physical disabilities often experience premature multimorbidity and adverse health events. A tailored primary care approach for this vulnerable population that also accounts for social and functional risk factors could promote healthier aging and more equitable health care.ObjectiveThis project will evaluate the implementation of a health program designed for people with physical disabilities. The proposed evaluation result is to generate the first best-practice protocol focused specifically on developing primary care to help reduce preventable causes of morbidity and improve functioning among people with physical disabilities.MethodsWe will design and implement a pilot health program for people with physical disabilities at a primary care clinic within Michigan Medicine. The health program for people with physical disabilities will be an integrated intervention involving a tailored best practice alert designed to prompt family medicine providers to screen and monitor for common, preventable health conditions. The program will also collect social and functional status information to determine the patient's need for further care coordination and support. Adult participants from this clinic with identified physical disabilities will be targeted for potential enrollment. To create a quasi-experimental setting, a separate departmental clinic will serve as a control site for comparison purposes. A quantitative analysis to estimate the treatment effect of implementing this health program will be conducted using a difference-in-differences approach. Outcomes of interest will include the use of preventative services (eg, hemoglobin A1c for diabetes screening), social work assistance, and emergency and hospital services. These data will be extracted from electronic health records. Time-invariant covariates, particularly sociodemographic covariates, will be included in the models. A qualitative analysis of patient and health care provider interviews will also be completed to assess the effect of the health program. Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scores will be assessed to both screen for depression and anxiety as well as explore program impacts related to addressing health and functioning needs related to physical disabilities in a primary care setting. These will be summarized through descriptive analyses.ResultsThis study was funded in September 2018, data collection started in September 2021, and data collection is expected to be concluded in September 2023.ConclusionsThis study is a mixed methods evaluation of the effectiveness of an integrated health program designed for people with physical disabilities, based on a quasi-experimental comparison between an intervention and a control clinic site. The intervention will be considered successful if it leads to improvements in greater use of screening and monitoring for preventable health conditions, increased social worker referrals to assist with health and functioning needs, and improvements in emergency and hospital-based services. The findings will help inform best practices for people with physical disabilities in a primary care setting.International registered report identifier (irrid)DERR1-10.2196/50105.

Project description:BackgroundHuman well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models. Thus, we conducted a randomised intervention study that focused on the effects of different types of training (endurance and strength) in previously physically inactive, healthy adults in comparison to controls that did not perform regular exercise. Overall study duration was ten weeks including six weeks of intervention period. In addition to 16S rRNA gene amplicon sequencing of longitudinally sampled faecal material of participants (six time points), detailed body composition measurements and analysis of blood samples (at baseline and after the intervention) were performed to obtain overall physiological changes within the intervention period. Activity tracker devices (wrist-band wearables) provided activity status and sleeping patterns of participants as well as exercise intensity and heart measurements.ResultsDifferent biometric responses between endurance and strength activities were identified, such as a significant increase of lymphocytes and decrease of mean corpuscular haemoglobin concentration (MCHC) only within the strength intervention group. In the endurance group, we observed a significant reduction in hip circumference and an increase in physical working capacity (PWC). Though a large variation of microbiota changes were observed between individuals of the same group, we did not find specific collective alterations in the endurance nor the strength groups, arguing for microbiome variations specific to individuals, and therefore, were not captured in our analysis.ConclusionsWe could show that different types of exercise have distinct but moderate effects on the overall physiology of humans and very distinct microbial changes in the gut. The observed overall changes during the intervention highlight the importance of physical activity on well-being. Future studies should investigate the effect of exercise on a longer timescale, investigate different training intensities and consider high-resolution shotgun metagenomics technology.Trial registrationDRKS, DRKS00015873 . Registered 12 December 2018; Retrospectively registered.

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Physical Activity as a Preventive Lifestyle Intervention Acts Through Specific Exosomal miRNA Species-Evidence From Human Short- and Long-Term Pilot Studies.

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