Researchers from an NIH-funded consortium are preparing to recruit nearly 2,600 participants whose data will be incorporated into maps of the molecular changes to the human body wrought by exercise—maps that may lead someday to greater use of personalized exercise regimens or exercise-mimetic drugs for people unable to exercise.
The National Institutes of Health-funded Molecular Transducers of Physical Activity Consortium (MoTrPAC) plans to measure molecular changes in healthy adults and children before, during, and after exercise, based on biospecimens provided by the volunteer participants. Adults will provide blood, fat, and muscle tissue samples, while children will provide only blood samples.
“MoTrPAC was launched to fill an important gap in exercise research,” NIH Director Francis S. Collins, M.D., Ph.D., said yesterday in a statement. “It shifts focus from a specific organ or disease, to a fundamental understanding of exercise at the molecular level—an understanding that may lead to personalized, prescribed exercise regimens based on an individual’s needs and traits.”
Recruitment of participants has been on hold due to safety concerns related to COVID-19, the NIH said, but will resume “when it is safe to do so.” When that occurs, MoTrPAC will recruit about 2,600 healthy volunteers ranging in age from 10 to 60-plus, and balanced between men and women, at 11 clinical sites nationwide.
In a study published Thursday in the journal Cell, MoTrPAC members said that samples will undergo in-depth analysis using technologies that include genomics, transcriptomics, DNA methylomics, targeted and untargeted proteomics, and targeted and untargeted metabolomics.
“When complete, MoTrPAC will deliver a map of the biological molecules and pathways underlying the systemic effects of acute and chronic exercise,” the consortium members wrote in Cell. “The data, which will ultimately be made freely available to the scientific community, will provide unprecedented opportunities to begin to understand the pathways by which physical activity influences health.
“In the future, it is expected that the knowledge gained will allow researchers and health professionals to develop personalized exercise recommendations and provide insights into molecular targets that could be manipulated to mimic some of the effects of exercise in persons unable to do so,” the MoTrPAC members added.
MoTrPAC members also detailed the Consortium’s approach to data gathering and shared results from an initial phase with a smaller group of adult volunteers and multiple rounds of preclinical studies in an animal model that were designed to set the stage for full-scale MoTrPAC clinical studies.
The preclinical research was also intended to enable MoTrPAC to generate data from tissues that cannot be collected from humans, expanding the scope of the consortium. Researchers at three preclinical animal study sites conducted both a single round of exercise and an exercise training regimen in young and aged rats. Following the exercise round, or after training, 19 biospecimens were collected per animal.
The biospecimens collected from the preclinical studies were sent to MoTrPAC’s biorepository, managed by the consortium’s coordinating center. The biospecimens also provided raw material for the study’s nine chemical analysis sites to generate data on exercise-responsive biomolecules like genes, indicators of gene activity, proteins, molecules involved in metabolism, and molecular signals in cell-to-cell communication.
The study’s planned genomic, epigenomic, and transcriptomic (GET) analyses wlll be designed to map and measure changes in:
- RNA transcriptome and transcript isoforms including small and micro RNA using RNA sequencing,
- DNA methylation and chromatin accessibility from rat and human tissues using reduced representation bisulfite (RRBS) for rat or methyl CpG hybrid capture for human specimens and ATAC-seq (assay for transposase-accessible chromatin with sequencing), respectively, and
- The genomic sequence and structure of all human participants.
Part of MoTrPAC’s study is designed to evaluate the body’s changing response to exercise after participants who begin the study as inactive complete a 12-week supervised exercise regimen. Sedentary adults will be randomly assigned to an endurance training regimen including treadmill and cycling activity, a resistance training regimen based on weightlifting, or an inactive control group. Low-activity children will be randomly assigned to an endurance training regimen, or to a control group where they pursue their normal activities.
A separate group of highly-active adults and youths will help researchers better understand molecular changes in participants who have exercised vigorously and consistently over an extended period of time, the NIH said.
MoTrPAC plans to recruit 270 children and adolescents (10–17 years of age) who are low-active in endurance-type exercise, and 1,980 healthy sedentary adults (age 18 years or greater) who will be medically screened and randomly assigned to endurance training (170 youth, 840 adults), resistance training (840 adults), or non-exercise control (50 youth, 300 adults).
An additional group of highly active endurance- (50 youth, 150 adults) and resistance- (150 adults) trained individuals will serve as comparators and will not participate in the MoTrPAC exercise training programs.
MoTrPAC is funded by the NIH Common Fund and overseen in collaboration with the NIH’s National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute of Diabetes and Digestive and Kidney Diseases.